Disc degeneration primarily contributes to chronic low back and neck pain.Consequently,there is an urgent need to understand the spectrum of disc degeneration phenotypes such as fibrosis,ectopic calcification,herniati...Disc degeneration primarily contributes to chronic low back and neck pain.Consequently,there is an urgent need to understand the spectrum of disc degeneration phenotypes such as fibrosis,ectopic calcification,herniation,or mixed phenotypes.Amongst these phenotypes,disc calcification is the least studied.Ectopic calcification,by definition,is the pathological mineralization of soft tissues,widely studied in the context of conditions that afflict vasculature,skin,and cartilage.Clinically,disc calcification is associated with poor surgical outcomes and back pain refractory to conservative treatment.It is frequently seen as a consequence of disc aging and progressive degeneration but exhibits unique molecular and morphological characteristics:hypertrophic chondrocyte-like cell differentiation;TNAP,ENPP1,and ANK upregulation;cell death;altered Pi and PPi homeostasis;and local inflammation.Recent studies in mouse models have provided a better understanding of the mechanisms underlying this phenotype.It is essential to recognize that the presentation and nature of mineralization differ between AF,NP,and EP compartments.Moreover,the combination of anatomic location,genetics,and environmental stressors,such as aging or trauma,govern the predisposition to calcification.Lastly,the systemic regulation of calcium and Pi metabolism is less important than the local activity of PPi modulated by the ANK-ENPP1 axis,along with disc cell death and differentiation status.While there is limited understanding of this phenotype,understanding the molecular pathways governing local intervertebral disc calcification may lead to developing disease-modifying drugs and better clinical management of degeneration-related pathologies.展开更多
BACKGROUND Conservative treatments have been reported to diminish or resolve clinical symptoms of lumbar intervertebral disc herniation(LIDH)within a few weeks.CASE SUMMARY Computed tomography and magnetic resonance i...BACKGROUND Conservative treatments have been reported to diminish or resolve clinical symptoms of lumbar intervertebral disc herniation(LIDH)within a few weeks.CASE SUMMARY Computed tomography and magnetic resonance imaging(MRI)of the lumbar region of a 25-yearold male diagnosed with LIDH showed prolapse of the L5/S2 disc.The disc extended 1.0 cm beyond the vertebral edge and hung along the posterior vertebral edge.The patient elected a conservative treatment regimen that included traditional Chinese medicine(TCM),acupuncture,and massage.During a follow-up period of more than 12 mo,good improvement in pain was reported without complications.MRI of the lumbar region after 12 mo showed obvious reabsorption of the herniation.CONCLUSION A conservative treatment regimen of TCM,acupuncture,and massage promoted reabsorption of a prolapsed disc.展开更多
Intervertebral disc(ID)degeneration(IDD)is one of the main causes of chronic low back pain,and degenerative lesions are usually caused by an imbalance between catabolic and anabolic processes in the ID.The environment...Intervertebral disc(ID)degeneration(IDD)is one of the main causes of chronic low back pain,and degenerative lesions are usually caused by an imbalance between catabolic and anabolic processes in the ID.The environment in which the ID is located is harsh,with almost no vascular distribution within the disc,and the nutrient supply relies mainly on the diffusion of oxygen and nutrients from the blood vessels located under the endplate.The stability of its internal environment also plays an important role in preventing IDD.The main feature of disc degeneration is a decrease in the number of cells.Mesenchymal stem cells have been used in the treatment of disc lesions due to their ability to differentiate into nucleus pulposus cells in a nonspecific anti-inflammatory manner.The main purpose is to promote their regeneration.The current aim of stem cell therapy is to replace the aged and metamorphosed cells in the ID and to increase the content of the extracellular matrix.The treatment of disc degeneration with stem cells has achieved good efficacy,and the current challenge is how to improve this efficacy.Here,we reviewed current treatments for disc degeneration and summarize studies on stem cell vesicles,enhancement of therapeutic effects when stem cells are mixed with related substances,and improvements in the efficacy of stem cell therapy by adjuvants under adverse conditions.We reviewed the new approaches and ideas for stem cell treatment of disc degeneration in order to contribute to the development of new therapeutic approaches to meet current challenges.展开更多
Objective To observe the influence of acupuncture on the post-operative rehabilitation in patients undergoing vertebral pulp extraction due to lumbar intervertebral disc protrusion (LIDP) so as to evaluate its effic...Objective To observe the influence of acupuncture on the post-operative rehabilitation in patients undergoing vertebral pulp extraction due to lumbar intervertebral disc protrusion (LIDP) so as to evaluate its efficacy in the treatment of lumbago induced by LIDP. Methods A total of 69 patients undergoing vertebral pulp extraction were randomized into acupuncture group ( n = 35) and control group ( n = 34). Patients of acupuncture group were treated with routine rehabilitation method and electroacupuncture (EA) stimulation on Zhìbiān (秩边 BL54) and Wěizhōng (委中 BL40), acupuncture on Shènshū ( 肾俞 BL23), Dàchángshū (大肠俞 BL25), BL54, BL40, Jiájǐ (夹脊 EX-B 2), Shàngliáo (上髎 BL31), etc., and cupping on BL40, with 15 days being a therapeutic course and for average 7. 36 courses. Patients of control group were treated with simple rehabilitation method. Functional recovery state was judged before and after surgery by using the standards of Japanese Orthopedic Association (JOA). Results The average recovery rates of 3 months, 6 months and one year after surgery were 49.93% ,90.31% and 95.08% separately in acupuncture group, and 26.24% ,63.42% and 71.36% successively in control group. The recovery rates of acupuncture group were significantly higher than those of control group at the same time-points (P〈0. 05). Conclusion Acupuncture has a definite effect on promoting post-operative functional recovery in LIDP patients undergoing vertebral pulp extraction and spinal fusion.展开更多
Objective:To provide anatomical datum for intrusive operations of lumbar intervertebral foramen,especially that using acupuncture-knife as intrusive tool.Methods:To dissect 10 antisepsis cadavers and observe the expos...Objective:To provide anatomical datum for intrusive operations of lumbar intervertebral foramen,especially that using acupuncture-knife as intrusive tool.Methods:To dissect 10 antisepsis cadavers and observe the exposed blood vessels,ligaments,nerves and their adjacent relations in L1/2~L5/S1intervertebral foramen.Results:Lumbar intervertebral foramen exit zones were almost sealed by nerves and blood vessels.There were two zones with relatively no blood vessel and nerve(triangular working zones)located in the midpoint of the distance between two adjacent roots of transverse processus,and clung to lamina of vertebral arch,and they were also found upon the margo superior of the root of transverse processus,but the ascending lumbar vein or(and)the rami anastomoticus between the remi inferior of intervertebral vein and lumbar veins were observed in 12%triangular working zones upon the margo superior of root of transverse processus.Conclusions:"Triangular working zone"was relatively avascular zone.Pay attention to the possibilty of presence of blood vessels on the entrance passage of intrusive operations on lumbar side rear.The needlepoint should be pierced at the midpoint of the distance between two adjacent roots of transverse processus and cling to the outer edge of lamina of vertebral arch when doing the foraminal lumbar puncture.As lumbar intervertebral foramina exit zone was almost sealed by nerves and blood vessels,blind incising and debonding with acupuncture-knife in this area was relatively much more dangerous.展开更多
Objective:To investigate the mechanism of expression and significance of vascular endothelial growth factor(VEGF) and p53 in degenerate intervertebral disc tissue.Methods:Pathological sections collected from 156 patie...Objective:To investigate the mechanism of expression and significance of vascular endothelial growth factor(VEGF) and p53 in degenerate intervertebral disc tissue.Methods:Pathological sections collected from 156 patienls with lumbar disc herniation after surgery were tested by immunohistochemistry method,for evaluation of the expression of VEGF and p53 in degenerate intervertebral disc tissue.Results:98 cases(62.8%) with vascular infiltration phenomenon are found,and positive rates of VEGF and p53 in degenerate intervertebral disc tissue are 73.42% (116/156) and 58.97%(92/156);co-expression rate is 53.2%(83/l56);the expression rates of VEFG and p53 are significantly higher in the tissue with blood vessel infiltration than in the tissue without infiltration;there is a close relationship of VEGF with p53.Conclusions:VEGF and p53 gene synergetic express in degenerate intervertebral disc tissue,working together in neovascularization and infiltration,and accelerating intervertebral disc tissue degeneration.展开更多
Most studies on spinal cord neuronal injury have focused on spinal cord tissue histology and the expression of nerve cell damage and repair-related genes. The importance of the microcirculation is often ignored in spi...Most studies on spinal cord neuronal injury have focused on spinal cord tissue histology and the expression of nerve cell damage and repair-related genes. The importance of the microcirculation is often ignored in spinal cord injury and repair research. Therefore, in this study, we established a rat model of intervertebral disc extrusion by inserting a silica gel pad into the left ventral sur-face of T13. Electroacupuncture was used to stimulate the bilateralZusanlipoint (ST36) and Neiting point (ST44) for 14 days. Compared with control animals, blood lfow in the ifrst lumbar vertebra (L1) was noticeably increased in rats given electroacupuncture. Microvessel density in the T13 segment of the spinal cord was increased significantly as well. The number of normal neurons was higher in the ventral horn of the spinal cord. In addition, vacuolation in the white matter was lessened. No obvious glial cell proliferation was visible. Furthermore, hindlimb motor function was improved signiifcantly. Collectively, our results suggest that electroacupuncture can improve neuronal morphology and microcirculation, and promote the recovery of neurological functions in a rat model of intervertebral disc extrusion.展开更多
Intervertebral disc regeneration field is rapidly growing since disc disorders represent a major health problem in industrialized countries with very few possible treatments.Indeed, current available therapies are sym...Intervertebral disc regeneration field is rapidly growing since disc disorders represent a major health problem in industrialized countries with very few possible treatments.Indeed, current available therapies are symptomatic, and surgical procedures consist in disc removal and spinal fusion, which is not immune to regardable concerns about possible comorbidities, cost-effectiveness, secondary risks and long-lasting outcomes. This review paper aims to share recent advances in stem cell therapy for the treatment of intervertebral disc degeneration. In literature the potential use of different adult stem cells for intervertebral disc regeneration has already been reported. Bone marrow mesenchymal stromal/stem cells, adipose tissue derived stem cells, synovial stem cells, muscle-derived stem cells, olfactory neural stem cells, induced pluripotent stem cells, hematopoietic stem cells, disc stem cells, and embryonic stem cells have been studied for this purpose either in vitro or in vivo. Moreover, several engineered carriers(e.g., hydrogels), characterized by full biocompatibility and prompt biodegradation, have been designed and combined with different stem cell types in order to optimize the local and controlled delivery of cellular substrates in situ. The paper overviews the literature discussing the current status of our knowledge of the different stem cells types used as a cell-based therapy for disc regeneration.展开更多
Intervertebral disc (IVD) degeneration is the leading cause of disability with no disease-modifying treatment. IVD degeneration is associated with instable mechanical loading in the spine, but little is known about ...Intervertebral disc (IVD) degeneration is the leading cause of disability with no disease-modifying treatment. IVD degeneration is associated with instable mechanical loading in the spine, but little is known about how mechanical stress regulates nucleus notochordal (NC) cells to maintain IVD homeostasis. Here we report that mechanical stress can result in excessive integrin αvβ6-mediated activation of transforming growth factor beta (TGFβ), decreased NC cell vacuoles, and increased matrix proteoglycan production, and results in degenerative disc disease (DDD). Knockout of TGFβ type II receptor (TβRII) or integrin αv in the NC cells inhibited functional activity of postnatal NC cells and also resulted in DDD under mechanical loading. Administration of RGD peptide, TGFβ, and αvβ6-neutralizing antibodies attenuated IVD degeneration. Thus, integrin-mediated activation of TGFβ plays a critical role in mechanical signaling transduction to regulate IVD cell function and homeostasis. Manipulation of this signaling pathway may be a potential therapeutic target to modify DDD.展开更多
Low back pain has become more prevalent in recent years,causing enormous economic burden for society and government.Common therapies used in clinics including conservative treatment and surgery can only relieve pain.S...Low back pain has become more prevalent in recent years,causing enormous economic burden for society and government.Common therapies used in clinics including conservative treatment and surgery can only relieve pain.Subsequent cell-based treatment such as mesenchymal stem cell transplantation poses problems such as short duration of therapeutic effect and tumorigenesis.Recently,the discovery and identification of stem cell niche and stem/progenitor cells in intervertebral disc bring increased attention to endogenous repair strategy.Therefore,we review the studies involving endogenous repair strategy and present the characteristics and current status of this treatment.Meanwhile,we also discuss the strategy and perspective of endogenous repair strategy in future.展开更多
Objective:To discuss the expression and significance of vascular endothelial growth factor (VEGF) and p53 expression in rat degenerated intervertebral disc(IVD) tissues.Methods:A total of 78 even-aged Sprague-Dawley(S...Objective:To discuss the expression and significance of vascular endothelial growth factor (VEGF) and p53 expression in rat degenerated intervertebral disc(IVD) tissues.Methods:A total of 78 even-aged Sprague-Dawley(SD) rats(observation group) were chosen to establish a rat IVD degeneration model with anterior limbs and tail-removing method.Three months after modeling, rats were executed and degenerated IVD tissues were obtained for pathological biopsy so as to observe VEGF and p53 expression thereof.Meanwhile,IVD tissues from 8 healthy rats were gained for comparison.Results:Capillary infiltration was found in 62.8%of cases in observation group. Positive expression of VEGF and p53 was seen in 74.4%and 59.0%of cases respectively with a co-expression rate of 53.8%.VECF and p53 expression in degenerated IVD tissues with capillary infiltration was higher than that in non-infiltration group(P【0.05).Conclasion:A coordinate expression of VEGF and p53 in rat degenerated IVD tissues is demonstrated,indicating that they are both involved in neovascularization and infiltration,which accelerates IVD degeneration.展开更多
Objective:To investigate the effect of osteoporosis and intervertebral disc degeneration on the endplate cartilage injury in rats.Methods:A total of 48 female Sprague Dawley rats(3 months)were randomly divided into Gr...Objective:To investigate the effect of osteoporosis and intervertebral disc degeneration on the endplate cartilage injury in rats.Methods:A total of 48 female Sprague Dawley rats(3 months)were randomly divided into Groups A,B,C and D with 12 rats in each group.Osteoporosis and intervertebral disc degeneration composite model,simple degeneration model and simple osteoporosis model were prepared in Groups A,B and C respectively.After modeling,four rats of each group at 12th.18th and 24th week were sacrificed,Intervertebral height of cervical vertebra C6/C7 was measured.Micro-CT was used to image the endplate of cephalic and caudal cartilage at C6/C7 intervertebral disc.Abraded area rate of C6 caudal and C7 cephalic cartilage endplate was calculated,and then C6/C7 intervertebral disc was routinely embedded and sectioned.stained with safranin O to observe histological changes microscopically.Results:At 12,18 and24 weeks,intervertebral disc height of C6/C7 were(0.58±0.09)mm,(0.53±0.04)mm and(0.04±0.06)mm in Group A rats,(0.55±0.05)mm,(0.52±0.07)mm and(0.07±0.05)mm in Group B rats.At 24th week.intervertebral disc height of Group A rats was significantly lower than that of Group B rats(P<0.05);intervertebral disc height of Groups A and B rats at each time point were significantly lower than that of Groups C and D(P<0.05).There was no significantly statistical difference of intervertebral disc height between Groups C and D(P>0.05).At 12 and 18 weeks,the abraded rate of C6 caudal and C7 cephalic cartilage endplate in Group A rats were significantly higher than that in Groups B.C and D rats(P<0.05);the abraded rate in Group B was significantly higher than that in Groups C and D(P>0.05).Microscopic observation of CT showed that ventral defects in C6caudal or C7 cephalic cartilage endplate in Groups A and B appeared after 12 weeks of modeling;obvious cracks were found in front of the C6 and C7 vertebral body,and cartilage defect shown the trend of"repairing"at 18 and 24 weeks after modeling.Conclusions:Intervertebral disc degeneration and osteoporosis can cause damage to the cartilage endplate.Co-existence of these two factors can induce more serious damage to the endplate.which has possitive correlation with intervertebral disc degeneration.Osteoporosis plays a certain role in intervertebral disc degeneration process,and accelerates the degeneration of intervertebral disc in a specific time window.展开更多
The aim of the present study was to compare the relationship of morphologically defined non-bulging/herni-ated, bulging and herniated intervertebral lumbar discs with quantitative apparent diffusion coefficient (ADC...The aim of the present study was to compare the relationship of morphologically defined non-bulging/herni-ated, bulging and herniated intervertebral lumbar discs with quantitative apparent diffusion coefficient (ADC). Thirty-two healthy volunteers and 28 patients with back pain or sciatica were examined by MRI. All intervertebral lumbar discs from L1 to S1 were classified according to morphological abnormality and degenerated grades. The ADC values of nucleus pulposus (NP) were measured and recorded. The significant differences about mean ADC values of NP were found between non-bulging/herniated discs and bulging discs as well as herniated discs (P 0.05), whereas there were no significant differences in ADC values between bulging and herniated discs (P 0.05). Moreover, statistically significant relationship was found in the mean ADC values of NP between "non-bulging/herniated and non-degenerated discs" and "non-bulging/herniated degenerated discs" as well as herniated discs (P 0.05). Linear regression analysis between ADC value and disc level revealed an inverse correlation (r = -0.18). The ADC map of the NP is a potentially useful tool for the quantitative assessment of componential and molecular alterations accompanied with lumbar disc abnormalities.展开更多
Due to the ethical concern and inability to detect inner stress distributions of intervertebral disc(IVD),traditional methods for investigation of intervertebral disc degeneration(IVDD)have significant limitations.Man...Due to the ethical concern and inability to detect inner stress distributions of intervertebral disc(IVD),traditional methods for investigation of intervertebral disc degeneration(IVDD)have significant limitations.Many researchers have demonstrated that finite element analysis(FEA)is an effective tool for the research of IVDD.However,the specific application of FEA for investigation of IVDD has not been systematically elucidated before.In the present review,we summarize the current finite element models(FEM)used for the investigation of IVDD,including the poroelastic non linear FEM,difTusive-reactive theory model and cell-activity coupled mechano-electrochemical theory model.We further elaborate the use of FEA for the research of IVDD pathogenesis especially for nutrition and biomechanics associated etiology,and the biological,biomechanical and clinical influences of IVDD.In addition,the application of FEA for evaluation and exploration of various treatments for IVDD is also elucidated.We conclude that FEA is an excellent technique for research of IVDD,which could be used to explore the etiology,biology and biomechanics of IVDD.In the future,FEA may help us to achieve the goal of individualized precision therapy.展开更多
Intervertebral disc(IVD)degenerative diseases are a common problem in the world,and they cause substantial social and economic burdens for people.The current methods for treating IVD degenerative diseases mainly inclu...Intervertebral disc(IVD)degenerative diseases are a common problem in the world,and they cause substantial social and economic burdens for people.The current methods for treating IVD degenerative diseases mainly include surgery and conservative treatment,which cannot fundamentally restore the normal structure of the disc.With continuous research on the mechanism of degeneration and the development of regenerative medicine,rapid progress has been made in the field of regenerative medicine regarding the use of stem cell-derived exosomes,which are active biological substances used in intercellular communication,because they show a strong effect in promoting tissue regeneration.The study of exosomes in the field of IVD degeneration has just begun,and many surprising achievements have been made.This paper mainly reviews the biological characteristics of exosomes and highlights the current status of exosomes in the field of IVD degeneration,as well as future developments regarding exosomes.展开更多
Objective: To assess the effects of axial vibrations on gene expression and lumbar intervertebral disc degeneration in vivo. Methods: A modified bipedal rat model was established using a brachial plexus rhizotomy appr...Objective: To assess the effects of axial vibrations on gene expression and lumbar intervertebral disc degeneration in vivo. Methods: A modified bipedal rat model was established using a brachial plexus rhizotomy approach to imitate human upright posture. The experimental animals were randomly divided into three groups: control, vertical vibration, and whole-body vibration. Gene expression in degeneration of the intervertebral discs was assessed by reverse transcription-quantitative polymerase chain reaction. Results: The expression of aggrecan, Col1α1, Col2α1, and decorin were shown to be up-regulated in 14-week-old rats in the vertical vibration and whole-body vibration groups, whereas biglycan and versican expression was down-regulated in 14-week-old rats of the two experimental groups. Furthermore, biglycan and versican expression levels were shown to be lower in the whole-body vibration group than in the vertical vibration group(P<0.05). Conclusions: This in-vivo study demonstrated that vibrations can influence the expression of anabolic genes. Furthermore, whole-body vibrations seem to have a greater effect in this regard than vertical vibrations. A new method is expected to relieve the low back pain of the patients through our research.展开更多
Karacoline is a compound found in the plant Aconitum kusnezoffii Reichb.Although Aconitum kusnezoffii Reichb is widely used for the treatment of pain,very few studies have been carried out on the use of karacoline due...Karacoline is a compound found in the plant Aconitum kusnezoffii Reichb.Although Aconitum kusnezoffii Reichb is widely used for the treatment of pain,very few studies have been carried out on the use of karacoline due to its potential toxicity.In this study,we selected key matrix metalloproteinases(MMPs),collagen II,and aggrecan as targets due to their association with intervertebral disc degeneration(IDD).Using these targets,we then used network pharmacology to predict a series of molecules that might exert therapeutic effects on IDD.Of these molecules,karacoline was predicted to have the best effect.Tumor necrosis factor(TNF)-a is known to promote the degeneration of the extracellular matrix in IDD.We therefore applied different concentrations of karacoline(0,1.25,or 12.88 mM)along with 100 ng/mL TNF-a to rat nucleus pulposus cells and found that karacoline reduced the expression of MMP-14 in IDD by inhibiting the nuclear factor(NF)-κB pathway,while collagen II and aggrecan expression was increased.This suggested that extracellular matrix degradation was inhibited by karacoline(P<0.05).Our data therefore reveal a new clinical application of karacoline and provide support for the use of network pharmacology in predicting novel drugs.展开更多
Back pain is a common condition with a high social impact and represents a global health burden.Intervertebral disc disease(IVDD)is one of the major causes of back pain;no therapeutics are currently available to rever...Back pain is a common condition with a high social impact and represents a global health burden.Intervertebral disc disease(IVDD)is one of the major causes of back pain;no therapeutics are currently available to reverse this disease.The impact of bone mineral density(BMD)on IVDD has been controversial,with some studies suggesting osteoporosis as causative for IVDD and others suggesting it as protective for IVDD.Functional studies to evaluate the influence of genetic components of BMD in IVDD could highlight opportunities for drug development and repurposing.By taking a holistic 3D approach,we established an aging zebrafish model for spontaneous IVDD.Increased BMD in aging,detected by automated computational analysis,is caused by bone deformities at the endplates.However,aged zebrafish spines showed changes in bone morphology,microstructure,mineral heterogeneity,and increased fragility that resembled osteoporosis.Elements of the discs recapitulated IVDD symptoms found in humans:the intervertebral ligament(equivalent to the annulus fibrosus)showed disorganized collagen fibers and herniation,while the disc center(nucleus pulposus equivalent)showed dehydration and cellular abnormalities.We manipulated BMD in young zebrafish by mutating sp7 and cathepsin K,leading to low and high BMD,respectively.Remarkably,we detected IVDD in both groups,demonstrating that low BMD does not protect against IVDD,and we found a strong correlation between high BMD and IVDD.Deep learning was applied to high-resolution synchrotron\iCJ image data to analyze osteocyte 3D lacunar distribution and morphology,revealing a role of sp7 in controlling the osteocyte lacunar 3D profile.Our findings suggest potential avenues through which bone quality can be targeted to identify beneficial therapeutics for IVDD.展开更多
BACKGROUND Thoracic intervertebral foramen puncture is the key step for interventional therapy on the thoracic nerve roots or dorsal root ganglia.The anatomical features of the thoracic spine are complex,and puncture ...BACKGROUND Thoracic intervertebral foramen puncture is the key step for interventional therapy on the thoracic nerve roots or dorsal root ganglia.The anatomical features of the thoracic spine are complex,and puncture injury to the pleura,blood vessels,spinal cord,and other tissues may cause serious complications.The spatial anatomical characteristics and related parameters for thoracic intervertebral foramen puncture remain poorly understood.AIM To observe and summarize the spatially applied anatomical characteristics for intervertebral foramen puncture on different vertebral segments.METHODS A total of 88 patients(41 males and 47 females)who underwent thoracic minimally invasive interventional treatment at Nanjing Drum Tower Hospital from January 2019 to June 2020 were included.Computed tomography images of 167 thoracic vertebral segments scanned in the prone position were collected.The width of the intertransverse space(D_(P)),the height of the rib neck/head above the lower transverse process(D_(R)),the width of the lateral border of the articular process/lamina(W_(P)),and the width of the posterior border of the vertebral body(W_(V))were measured.At the upper 1/3 of the intervertebral foramina,the horizontal inclination angle(α)from the lateral border of the articular process/lamina to the posterolateral border of the vertebral body was measured.The ratios D_(R)/D_(P) and W_(P)/W_(V) were calculated.The intervertebral foramen parameters were compared between segments.RESULTS No rib head/neck occlusion(D_(R)/D_(P)>0)was found in the intertransverse spaces of T1-2 and T12-L1.The incidence of occlusion for the upper thoracic segments(T1-5,n=138),middle thoracic segments(T5-9,n=116),and lower thoracic segments(T9-L1,n=80)were 76.81%,100%,and 82.50%,respectively.The incidence of occlusion for the middle thoracic segments was significantly higher than that for the upper and lower thoracic segments(P<0.05).The incidence of>1/2 occlusion(D_(R)/D_(P)>1/2)for the upper,middle,and lower thoracic segments was 7.97%,74.14%,and 32.50%,respectively.The incidence of>1/2 occlusion for the middle thoracic segments was significantly higher than that for the upper and lower thoracic segments(P<0.05).W_(P) was longer than W_(V) on T1-2 to T9-10 and shorter than W_(V) on T10-11 to T12-L1.The horizontal puncture angle(α)into the external opening of the intervertebral foramina was positively correlated with the segments of the thoracic vertebrae from the cephalic to caudal portion(left:r=0.772,P<0.01;right:r=0.771,P<0.01),and the horizontal inclination angle for T11-12 and T12-L1 was 90°.CONCLUSION It is necessary to identify the spatial impact of the rib head/neck on the puncture path of the intervertebral foramina and design appropriate puncture angles for different segments.展开更多
Lumbar degenerative disc diseases cause low back pain(LBP). The maintenance of the height and stability of the intervertebral disc(IVD) space is an effective treatment for LBP. The following study evaluated the effect...Lumbar degenerative disc diseases cause low back pain(LBP). The maintenance of the height and stability of the intervertebral disc(IVD) space is an effective treatment for LBP. The following study evaluated the effects of fibroblast injection on intervertebral disc degeneration(IDD) in a preclinical setting. Compared with the IDD group, the fibroblast treatment group demonstrated effective maintenance of IVD height, reduced endplate degeneration, and improved nuclear magnetic resonance signals and overall histological structure. In doing so, fibrotic IVDs maintained the stability and biomechanics of the vertebra. This finding is in agreement with clinical findings that human nucleus pulposus(NP) fibrosis is essential for the maintenance of IVD height and mechanical properties in patients following percutaneous endoscopic lumbar discectomy(PELD). Mechanistically, we demonstrated that injected fibroblasts not only proliferated but also induced NP cells to adopt a fibrotic phenotype via the secretion of TGF-β.Finally, to better mimic human conditions, the efficacy of autologous fibroblast injection in the treatment of IDD was further examined in a nonhuman primate cynomolgus monkey model due to their capacity for upright posture. We showed that the injection of fibroblasts could maintain the IVD height and rescue IVD signals in cynomolgus monkeys. Taken together, the results of our study reveal that autologous fibroblast injection can enhance the natural process of fibrosis during acute and subacute stages of stress-induced IDD. Fibrotic IVDs can maintain the stability, biological activity, and mechanical properties of the intervertebral space, thus providing a new direction for the treatment of intervertebral space-derived lumbar degenerative diseases.展开更多
基金support by R01AR055655, R01AR074813, and R01AG073349 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and the National Institute on Aging (NIA)supported by PXE International.
文摘Disc degeneration primarily contributes to chronic low back and neck pain.Consequently,there is an urgent need to understand the spectrum of disc degeneration phenotypes such as fibrosis,ectopic calcification,herniation,or mixed phenotypes.Amongst these phenotypes,disc calcification is the least studied.Ectopic calcification,by definition,is the pathological mineralization of soft tissues,widely studied in the context of conditions that afflict vasculature,skin,and cartilage.Clinically,disc calcification is associated with poor surgical outcomes and back pain refractory to conservative treatment.It is frequently seen as a consequence of disc aging and progressive degeneration but exhibits unique molecular and morphological characteristics:hypertrophic chondrocyte-like cell differentiation;TNAP,ENPP1,and ANK upregulation;cell death;altered Pi and PPi homeostasis;and local inflammation.Recent studies in mouse models have provided a better understanding of the mechanisms underlying this phenotype.It is essential to recognize that the presentation and nature of mineralization differ between AF,NP,and EP compartments.Moreover,the combination of anatomic location,genetics,and environmental stressors,such as aging or trauma,govern the predisposition to calcification.Lastly,the systemic regulation of calcium and Pi metabolism is less important than the local activity of PPi modulated by the ANK-ENPP1 axis,along with disc cell death and differentiation status.While there is limited understanding of this phenotype,understanding the molecular pathways governing local intervertebral disc calcification may lead to developing disease-modifying drugs and better clinical management of degeneration-related pathologies.
基金Supported by National Nature Science Foundation of China,No.82004495Natural Science Foundation of Shandong Province,China,No.ZR2020QH318+1 种基金The 69th batch of a grant from China Postdoctoral Foundation,No.2021M691985Taishan Scholars Young Experts Program,China,No.tsqn202211349.
文摘BACKGROUND Conservative treatments have been reported to diminish or resolve clinical symptoms of lumbar intervertebral disc herniation(LIDH)within a few weeks.CASE SUMMARY Computed tomography and magnetic resonance imaging(MRI)of the lumbar region of a 25-yearold male diagnosed with LIDH showed prolapse of the L5/S2 disc.The disc extended 1.0 cm beyond the vertebral edge and hung along the posterior vertebral edge.The patient elected a conservative treatment regimen that included traditional Chinese medicine(TCM),acupuncture,and massage.During a follow-up period of more than 12 mo,good improvement in pain was reported without complications.MRI of the lumbar region after 12 mo showed obvious reabsorption of the herniation.CONCLUSION A conservative treatment regimen of TCM,acupuncture,and massage promoted reabsorption of a prolapsed disc.
基金National Natural Science Foundation of China,No.82202766Natural Science Foundation of Hubei Province of China,No.2022CFB686+1 种基金Science Foundation of Union Hospital,No.2021xhyn102Scientific Research Training Program for Young Talents in Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,China.
文摘Intervertebral disc(ID)degeneration(IDD)is one of the main causes of chronic low back pain,and degenerative lesions are usually caused by an imbalance between catabolic and anabolic processes in the ID.The environment in which the ID is located is harsh,with almost no vascular distribution within the disc,and the nutrient supply relies mainly on the diffusion of oxygen and nutrients from the blood vessels located under the endplate.The stability of its internal environment also plays an important role in preventing IDD.The main feature of disc degeneration is a decrease in the number of cells.Mesenchymal stem cells have been used in the treatment of disc lesions due to their ability to differentiate into nucleus pulposus cells in a nonspecific anti-inflammatory manner.The main purpose is to promote their regeneration.The current aim of stem cell therapy is to replace the aged and metamorphosed cells in the ID and to increase the content of the extracellular matrix.The treatment of disc degeneration with stem cells has achieved good efficacy,and the current challenge is how to improve this efficacy.Here,we reviewed current treatments for disc degeneration and summarize studies on stem cell vesicles,enhancement of therapeutic effects when stem cells are mixed with related substances,and improvements in the efficacy of stem cell therapy by adjuvants under adverse conditions.We reviewed the new approaches and ideas for stem cell treatment of disc degeneration in order to contribute to the development of new therapeutic approaches to meet current challenges.
文摘Objective To observe the influence of acupuncture on the post-operative rehabilitation in patients undergoing vertebral pulp extraction due to lumbar intervertebral disc protrusion (LIDP) so as to evaluate its efficacy in the treatment of lumbago induced by LIDP. Methods A total of 69 patients undergoing vertebral pulp extraction were randomized into acupuncture group ( n = 35) and control group ( n = 34). Patients of acupuncture group were treated with routine rehabilitation method and electroacupuncture (EA) stimulation on Zhìbiān (秩边 BL54) and Wěizhōng (委中 BL40), acupuncture on Shènshū ( 肾俞 BL23), Dàchángshū (大肠俞 BL25), BL54, BL40, Jiájǐ (夹脊 EX-B 2), Shàngliáo (上髎 BL31), etc., and cupping on BL40, with 15 days being a therapeutic course and for average 7. 36 courses. Patients of control group were treated with simple rehabilitation method. Functional recovery state was judged before and after surgery by using the standards of Japanese Orthopedic Association (JOA). Results The average recovery rates of 3 months, 6 months and one year after surgery were 49.93% ,90.31% and 95.08% separately in acupuncture group, and 26.24% ,63.42% and 71.36% successively in control group. The recovery rates of acupuncture group were significantly higher than those of control group at the same time-points (P〈0. 05). Conclusion Acupuncture has a definite effect on promoting post-operative functional recovery in LIDP patients undergoing vertebral pulp extraction and spinal fusion.
文摘Objective:To provide anatomical datum for intrusive operations of lumbar intervertebral foramen,especially that using acupuncture-knife as intrusive tool.Methods:To dissect 10 antisepsis cadavers and observe the exposed blood vessels,ligaments,nerves and their adjacent relations in L1/2~L5/S1intervertebral foramen.Results:Lumbar intervertebral foramen exit zones were almost sealed by nerves and blood vessels.There were two zones with relatively no blood vessel and nerve(triangular working zones)located in the midpoint of the distance between two adjacent roots of transverse processus,and clung to lamina of vertebral arch,and they were also found upon the margo superior of the root of transverse processus,but the ascending lumbar vein or(and)the rami anastomoticus between the remi inferior of intervertebral vein and lumbar veins were observed in 12%triangular working zones upon the margo superior of root of transverse processus.Conclusions:"Triangular working zone"was relatively avascular zone.Pay attention to the possibilty of presence of blood vessels on the entrance passage of intrusive operations on lumbar side rear.The needlepoint should be pierced at the midpoint of the distance between two adjacent roots of transverse processus and cling to the outer edge of lamina of vertebral arch when doing the foraminal lumbar puncture.As lumbar intervertebral foramina exit zone was almost sealed by nerves and blood vessels,blind incising and debonding with acupuncture-knife in this area was relatively much more dangerous.
文摘Objective:To investigate the mechanism of expression and significance of vascular endothelial growth factor(VEGF) and p53 in degenerate intervertebral disc tissue.Methods:Pathological sections collected from 156 patienls with lumbar disc herniation after surgery were tested by immunohistochemistry method,for evaluation of the expression of VEGF and p53 in degenerate intervertebral disc tissue.Results:98 cases(62.8%) with vascular infiltration phenomenon are found,and positive rates of VEGF and p53 in degenerate intervertebral disc tissue are 73.42% (116/156) and 58.97%(92/156);co-expression rate is 53.2%(83/l56);the expression rates of VEFG and p53 are significantly higher in the tissue with blood vessel infiltration than in the tissue without infiltration;there is a close relationship of VEGF with p53.Conclusions:VEGF and p53 gene synergetic express in degenerate intervertebral disc tissue,working together in neovascularization and infiltration,and accelerating intervertebral disc tissue degeneration.
基金supported by the National Natural Science Foundation of China,No.31372473,30871886the Funding Project for Academic Human Resources Development in Institutions of Higher Learning under the Jurisdiction of Beijing Municipality of China,No.PHR201107134the 2012 Scientific Research Quality Raising Funds of Beijing University of Agriculture of China,No.PXM2012_014207_000010
文摘Most studies on spinal cord neuronal injury have focused on spinal cord tissue histology and the expression of nerve cell damage and repair-related genes. The importance of the microcirculation is often ignored in spinal cord injury and repair research. Therefore, in this study, we established a rat model of intervertebral disc extrusion by inserting a silica gel pad into the left ventral sur-face of T13. Electroacupuncture was used to stimulate the bilateralZusanlipoint (ST36) and Neiting point (ST44) for 14 days. Compared with control animals, blood lfow in the ifrst lumbar vertebra (L1) was noticeably increased in rats given electroacupuncture. Microvessel density in the T13 segment of the spinal cord was increased significantly as well. The number of normal neurons was higher in the ventral horn of the spinal cord. In addition, vacuolation in the white matter was lessened. No obvious glial cell proliferation was visible. Furthermore, hindlimb motor function was improved signiifcantly. Collectively, our results suggest that electroacupuncture can improve neuronal morphology and microcirculation, and promote the recovery of neurological functions in a rat model of intervertebral disc extrusion.
文摘Intervertebral disc regeneration field is rapidly growing since disc disorders represent a major health problem in industrialized countries with very few possible treatments.Indeed, current available therapies are symptomatic, and surgical procedures consist in disc removal and spinal fusion, which is not immune to regardable concerns about possible comorbidities, cost-effectiveness, secondary risks and long-lasting outcomes. This review paper aims to share recent advances in stem cell therapy for the treatment of intervertebral disc degeneration. In literature the potential use of different adult stem cells for intervertebral disc regeneration has already been reported. Bone marrow mesenchymal stromal/stem cells, adipose tissue derived stem cells, synovial stem cells, muscle-derived stem cells, olfactory neural stem cells, induced pluripotent stem cells, hematopoietic stem cells, disc stem cells, and embryonic stem cells have been studied for this purpose either in vitro or in vivo. Moreover, several engineered carriers(e.g., hydrogels), characterized by full biocompatibility and prompt biodegradation, have been designed and combined with different stem cell types in order to optimize the local and controlled delivery of cellular substrates in situ. The paper overviews the literature discussing the current status of our knowledge of the different stem cells types used as a cell-based therapy for disc regeneration.
文摘Intervertebral disc (IVD) degeneration is the leading cause of disability with no disease-modifying treatment. IVD degeneration is associated with instable mechanical loading in the spine, but little is known about how mechanical stress regulates nucleus notochordal (NC) cells to maintain IVD homeostasis. Here we report that mechanical stress can result in excessive integrin αvβ6-mediated activation of transforming growth factor beta (TGFβ), decreased NC cell vacuoles, and increased matrix proteoglycan production, and results in degenerative disc disease (DDD). Knockout of TGFβ type II receptor (TβRII) or integrin αv in the NC cells inhibited functional activity of postnatal NC cells and also resulted in DDD under mechanical loading. Administration of RGD peptide, TGFβ, and αvβ6-neutralizing antibodies attenuated IVD degeneration. Thus, integrin-mediated activation of TGFβ plays a critical role in mechanical signaling transduction to regulate IVD cell function and homeostasis. Manipulation of this signaling pathway may be a potential therapeutic target to modify DDD.
基金National Natural Science Foundation of China,No.81972136National Natural Science Foundation for Young Scholars of China,No.81401830+3 种基金Guangxi Natural Science Foundation General Project,No.2018JJA14775Young Medical Scholars Major Program of Jiangsu Province,No.QNRC2016342Innovation Team Project of Jiangsu Province,No.CXTDB2017004Key Funding Project of Maternal and Child Health Research of Jiangsu Province,No.F201801.
文摘Low back pain has become more prevalent in recent years,causing enormous economic burden for society and government.Common therapies used in clinics including conservative treatment and surgery can only relieve pain.Subsequent cell-based treatment such as mesenchymal stem cell transplantation poses problems such as short duration of therapeutic effect and tumorigenesis.Recently,the discovery and identification of stem cell niche and stem/progenitor cells in intervertebral disc bring increased attention to endogenous repair strategy.Therefore,we review the studies involving endogenous repair strategy and present the characteristics and current status of this treatment.Meanwhile,we also discuss the strategy and perspective of endogenous repair strategy in future.
文摘Objective:To discuss the expression and significance of vascular endothelial growth factor (VEGF) and p53 expression in rat degenerated intervertebral disc(IVD) tissues.Methods:A total of 78 even-aged Sprague-Dawley(SD) rats(observation group) were chosen to establish a rat IVD degeneration model with anterior limbs and tail-removing method.Three months after modeling, rats were executed and degenerated IVD tissues were obtained for pathological biopsy so as to observe VEGF and p53 expression thereof.Meanwhile,IVD tissues from 8 healthy rats were gained for comparison.Results:Capillary infiltration was found in 62.8%of cases in observation group. Positive expression of VEGF and p53 was seen in 74.4%and 59.0%of cases respectively with a co-expression rate of 53.8%.VECF and p53 expression in degenerated IVD tissues with capillary infiltration was higher than that in non-infiltration group(P【0.05).Conclasion:A coordinate expression of VEGF and p53 in rat degenerated IVD tissues is demonstrated,indicating that they are both involved in neovascularization and infiltration,which accelerates IVD degeneration.
基金supported by National Science Foundation.Grant No.81171764
文摘Objective:To investigate the effect of osteoporosis and intervertebral disc degeneration on the endplate cartilage injury in rats.Methods:A total of 48 female Sprague Dawley rats(3 months)were randomly divided into Groups A,B,C and D with 12 rats in each group.Osteoporosis and intervertebral disc degeneration composite model,simple degeneration model and simple osteoporosis model were prepared in Groups A,B and C respectively.After modeling,four rats of each group at 12th.18th and 24th week were sacrificed,Intervertebral height of cervical vertebra C6/C7 was measured.Micro-CT was used to image the endplate of cephalic and caudal cartilage at C6/C7 intervertebral disc.Abraded area rate of C6 caudal and C7 cephalic cartilage endplate was calculated,and then C6/C7 intervertebral disc was routinely embedded and sectioned.stained with safranin O to observe histological changes microscopically.Results:At 12,18 and24 weeks,intervertebral disc height of C6/C7 were(0.58±0.09)mm,(0.53±0.04)mm and(0.04±0.06)mm in Group A rats,(0.55±0.05)mm,(0.52±0.07)mm and(0.07±0.05)mm in Group B rats.At 24th week.intervertebral disc height of Group A rats was significantly lower than that of Group B rats(P<0.05);intervertebral disc height of Groups A and B rats at each time point were significantly lower than that of Groups C and D(P<0.05).There was no significantly statistical difference of intervertebral disc height between Groups C and D(P>0.05).At 12 and 18 weeks,the abraded rate of C6 caudal and C7 cephalic cartilage endplate in Group A rats were significantly higher than that in Groups B.C and D rats(P<0.05);the abraded rate in Group B was significantly higher than that in Groups C and D(P>0.05).Microscopic observation of CT showed that ventral defects in C6caudal or C7 cephalic cartilage endplate in Groups A and B appeared after 12 weeks of modeling;obvious cracks were found in front of the C6 and C7 vertebral body,and cartilage defect shown the trend of"repairing"at 18 and 24 weeks after modeling.Conclusions:Intervertebral disc degeneration and osteoporosis can cause damage to the cartilage endplate.Co-existence of these two factors can induce more serious damage to the endplate.which has possitive correlation with intervertebral disc degeneration.Osteoporosis plays a certain role in intervertebral disc degeneration process,and accelerates the degeneration of intervertebral disc in a specific time window.
基金supported by the National Natural Foundation of China (No.30970797)Shaanxi Science and Technology Plan Projects (No. 2008k09-1)
文摘The aim of the present study was to compare the relationship of morphologically defined non-bulging/herni-ated, bulging and herniated intervertebral lumbar discs with quantitative apparent diffusion coefficient (ADC). Thirty-two healthy volunteers and 28 patients with back pain or sciatica were examined by MRI. All intervertebral lumbar discs from L1 to S1 were classified according to morphological abnormality and degenerated grades. The ADC values of nucleus pulposus (NP) were measured and recorded. The significant differences about mean ADC values of NP were found between non-bulging/herniated discs and bulging discs as well as herniated discs (P 0.05), whereas there were no significant differences in ADC values between bulging and herniated discs (P 0.05). Moreover, statistically significant relationship was found in the mean ADC values of NP between "non-bulging/herniated and non-degenerated discs" and "non-bulging/herniated degenerated discs" as well as herniated discs (P 0.05). Linear regression analysis between ADC value and disc level revealed an inverse correlation (r = -0.18). The ADC map of the NP is a potentially useful tool for the quantitative assessment of componential and molecular alterations accompanied with lumbar disc abnormalities.
基金the National Key Research and Development Program of China(No.2016YFC1100100)Major Research Plan of National Natural Science Foundation of China(No.91649204).
文摘Due to the ethical concern and inability to detect inner stress distributions of intervertebral disc(IVD),traditional methods for investigation of intervertebral disc degeneration(IVDD)have significant limitations.Many researchers have demonstrated that finite element analysis(FEA)is an effective tool for the research of IVDD.However,the specific application of FEA for investigation of IVDD has not been systematically elucidated before.In the present review,we summarize the current finite element models(FEM)used for the investigation of IVDD,including the poroelastic non linear FEM,difTusive-reactive theory model and cell-activity coupled mechano-electrochemical theory model.We further elaborate the use of FEA for the research of IVDD pathogenesis especially for nutrition and biomechanics associated etiology,and the biological,biomechanical and clinical influences of IVDD.In addition,the application of FEA for evaluation and exploration of various treatments for IVDD is also elucidated.We conclude that FEA is an excellent technique for research of IVDD,which could be used to explore the etiology,biology and biomechanics of IVDD.In the future,FEA may help us to achieve the goal of individualized precision therapy.
文摘Intervertebral disc(IVD)degenerative diseases are a common problem in the world,and they cause substantial social and economic burdens for people.The current methods for treating IVD degenerative diseases mainly include surgery and conservative treatment,which cannot fundamentally restore the normal structure of the disc.With continuous research on the mechanism of degeneration and the development of regenerative medicine,rapid progress has been made in the field of regenerative medicine regarding the use of stem cell-derived exosomes,which are active biological substances used in intercellular communication,because they show a strong effect in promoting tissue regeneration.The study of exosomes in the field of IVD degeneration has just begun,and many surprising achievements have been made.This paper mainly reviews the biological characteristics of exosomes and highlights the current status of exosomes in the field of IVD degeneration,as well as future developments regarding exosomes.
基金supported by the National Natural Science Foundation of China(Grant No.81401768,81301646)the Natural Science Foundation of Jiangsu Province(Grant No.BK20140289)+1 种基金the Specialized Research Fund for the Doctoral Program of Higher Education of China(Grant No.20123201120018)China Postdoctoral Science Foundation on the 53rd general program(Grant No.2013M531404)
文摘Objective: To assess the effects of axial vibrations on gene expression and lumbar intervertebral disc degeneration in vivo. Methods: A modified bipedal rat model was established using a brachial plexus rhizotomy approach to imitate human upright posture. The experimental animals were randomly divided into three groups: control, vertical vibration, and whole-body vibration. Gene expression in degeneration of the intervertebral discs was assessed by reverse transcription-quantitative polymerase chain reaction. Results: The expression of aggrecan, Col1α1, Col2α1, and decorin were shown to be up-regulated in 14-week-old rats in the vertical vibration and whole-body vibration groups, whereas biglycan and versican expression was down-regulated in 14-week-old rats of the two experimental groups. Furthermore, biglycan and versican expression levels were shown to be lower in the whole-body vibration group than in the vertical vibration group(P<0.05). Conclusions: This in-vivo study demonstrated that vibrations can influence the expression of anabolic genes. Furthermore, whole-body vibrations seem to have a greater effect in this regard than vertical vibrations. A new method is expected to relieve the low back pain of the patients through our research.
文摘Karacoline is a compound found in the plant Aconitum kusnezoffii Reichb.Although Aconitum kusnezoffii Reichb is widely used for the treatment of pain,very few studies have been carried out on the use of karacoline due to its potential toxicity.In this study,we selected key matrix metalloproteinases(MMPs),collagen II,and aggrecan as targets due to their association with intervertebral disc degeneration(IDD).Using these targets,we then used network pharmacology to predict a series of molecules that might exert therapeutic effects on IDD.Of these molecules,karacoline was predicted to have the best effect.Tumor necrosis factor(TNF)-a is known to promote the degeneration of the extracellular matrix in IDD.We therefore applied different concentrations of karacoline(0,1.25,or 12.88 mM)along with 100 ng/mL TNF-a to rat nucleus pulposus cells and found that karacoline reduced the expression of MMP-14 in IDD by inhibiting the nuclear factor(NF)-κB pathway,while collagen II and aggrecan expression was increased.This suggested that extracellular matrix degradation was inhibited by karacoline(P<0.05).Our data therefore reveal a new clinical application of karacoline and provide support for the use of network pharmacology in predicting novel drugs.
文摘Back pain is a common condition with a high social impact and represents a global health burden.Intervertebral disc disease(IVDD)is one of the major causes of back pain;no therapeutics are currently available to reverse this disease.The impact of bone mineral density(BMD)on IVDD has been controversial,with some studies suggesting osteoporosis as causative for IVDD and others suggesting it as protective for IVDD.Functional studies to evaluate the influence of genetic components of BMD in IVDD could highlight opportunities for drug development and repurposing.By taking a holistic 3D approach,we established an aging zebrafish model for spontaneous IVDD.Increased BMD in aging,detected by automated computational analysis,is caused by bone deformities at the endplates.However,aged zebrafish spines showed changes in bone morphology,microstructure,mineral heterogeneity,and increased fragility that resembled osteoporosis.Elements of the discs recapitulated IVDD symptoms found in humans:the intervertebral ligament(equivalent to the annulus fibrosus)showed disorganized collagen fibers and herniation,while the disc center(nucleus pulposus equivalent)showed dehydration and cellular abnormalities.We manipulated BMD in young zebrafish by mutating sp7 and cathepsin K,leading to low and high BMD,respectively.Remarkably,we detected IVDD in both groups,demonstrating that low BMD does not protect against IVDD,and we found a strong correlation between high BMD and IVDD.Deep learning was applied to high-resolution synchrotron\iCJ image data to analyze osteocyte 3D lacunar distribution and morphology,revealing a role of sp7 in controlling the osteocyte lacunar 3D profile.Our findings suggest potential avenues through which bone quality can be targeted to identify beneficial therapeutics for IVDD.
基金Supported by The Key R&D Project in Jiangsu Province,No.BE2017603 and No.BE2017675the Key Program of Medical Science and Technology Development Projects in Nanjing,No.ZKX19016.
文摘BACKGROUND Thoracic intervertebral foramen puncture is the key step for interventional therapy on the thoracic nerve roots or dorsal root ganglia.The anatomical features of the thoracic spine are complex,and puncture injury to the pleura,blood vessels,spinal cord,and other tissues may cause serious complications.The spatial anatomical characteristics and related parameters for thoracic intervertebral foramen puncture remain poorly understood.AIM To observe and summarize the spatially applied anatomical characteristics for intervertebral foramen puncture on different vertebral segments.METHODS A total of 88 patients(41 males and 47 females)who underwent thoracic minimally invasive interventional treatment at Nanjing Drum Tower Hospital from January 2019 to June 2020 were included.Computed tomography images of 167 thoracic vertebral segments scanned in the prone position were collected.The width of the intertransverse space(D_(P)),the height of the rib neck/head above the lower transverse process(D_(R)),the width of the lateral border of the articular process/lamina(W_(P)),and the width of the posterior border of the vertebral body(W_(V))were measured.At the upper 1/3 of the intervertebral foramina,the horizontal inclination angle(α)from the lateral border of the articular process/lamina to the posterolateral border of the vertebral body was measured.The ratios D_(R)/D_(P) and W_(P)/W_(V) were calculated.The intervertebral foramen parameters were compared between segments.RESULTS No rib head/neck occlusion(D_(R)/D_(P)>0)was found in the intertransverse spaces of T1-2 and T12-L1.The incidence of occlusion for the upper thoracic segments(T1-5,n=138),middle thoracic segments(T5-9,n=116),and lower thoracic segments(T9-L1,n=80)were 76.81%,100%,and 82.50%,respectively.The incidence of occlusion for the middle thoracic segments was significantly higher than that for the upper and lower thoracic segments(P<0.05).The incidence of>1/2 occlusion(D_(R)/D_(P)>1/2)for the upper,middle,and lower thoracic segments was 7.97%,74.14%,and 32.50%,respectively.The incidence of>1/2 occlusion for the middle thoracic segments was significantly higher than that for the upper and lower thoracic segments(P<0.05).W_(P) was longer than W_(V) on T1-2 to T9-10 and shorter than W_(V) on T10-11 to T12-L1.The horizontal puncture angle(α)into the external opening of the intervertebral foramina was positively correlated with the segments of the thoracic vertebrae from the cephalic to caudal portion(left:r=0.772,P<0.01;right:r=0.771,P<0.01),and the horizontal inclination angle for T11-12 and T12-L1 was 90°.CONCLUSION It is necessary to identify the spatial impact of the rib head/neck on the puncture path of the intervertebral foramina and design appropriate puncture angles for different segments.
基金supported by the National Natural Science Foundation of China (81871790) & (81572167)the Shanghai Hospital Development Center Foundation (SHDC12016110)
文摘Lumbar degenerative disc diseases cause low back pain(LBP). The maintenance of the height and stability of the intervertebral disc(IVD) space is an effective treatment for LBP. The following study evaluated the effects of fibroblast injection on intervertebral disc degeneration(IDD) in a preclinical setting. Compared with the IDD group, the fibroblast treatment group demonstrated effective maintenance of IVD height, reduced endplate degeneration, and improved nuclear magnetic resonance signals and overall histological structure. In doing so, fibrotic IVDs maintained the stability and biomechanics of the vertebra. This finding is in agreement with clinical findings that human nucleus pulposus(NP) fibrosis is essential for the maintenance of IVD height and mechanical properties in patients following percutaneous endoscopic lumbar discectomy(PELD). Mechanistically, we demonstrated that injected fibroblasts not only proliferated but also induced NP cells to adopt a fibrotic phenotype via the secretion of TGF-β.Finally, to better mimic human conditions, the efficacy of autologous fibroblast injection in the treatment of IDD was further examined in a nonhuman primate cynomolgus monkey model due to their capacity for upright posture. We showed that the injection of fibroblasts could maintain the IVD height and rescue IVD signals in cynomolgus monkeys. Taken together, the results of our study reveal that autologous fibroblast injection can enhance the natural process of fibrosis during acute and subacute stages of stress-induced IDD. Fibrotic IVDs can maintain the stability, biological activity, and mechanical properties of the intervertebral space, thus providing a new direction for the treatment of intervertebral space-derived lumbar degenerative diseases.