Background:Bone stress injuries(BSIs)are common in female runners,and recurrent BSI rates are high.Previous work suggests an association between higher impact loading during running and tibial BSI.However,it is unknow...Background:Bone stress injuries(BSIs)are common in female runners,and recurrent BSI rates are high.Previous work suggests an association between higher impact loading during running and tibial BSI.However,it is unknown whether impact loading and fatigue-related loading changes discriminate women with a history of multiple BSIs.This study compared impact variables at the beginning of a treadmill run to exertion andthe changes in those variables with exertion among female runners with no history of BSI as well as among those with a history of single or multiple BSIs.Methods:We enrolled 45 female runners(aged 18-40 years)for this cross-sectional study:having no history of diagnosed lower extremity BSI(N-BSI,n=14);a history of 1 lower extremity BSI(1-BSI,n=16);and diagnosed by imaging,or a history of multiple(>3)lower extremity BSIs(M-BSI,n=15).Participants completed a 5-km race speed run on an instrumented treadmill while wearing an Inertial Measurement Unit.The vertical average loading rate(VALR),vertical instantaneous loading rate(VILR),vertical stiffness during impact via instrumented treadmill,and tibial shock determined as the peak po sitive tibial acceleration via Inertial Measurement Unit were measured at the beginning and the end of the run.Results:There were no differences between groups in VALR,VILR,vertical stiffness,or tibial shock in a fresh or exerted condition.However,compared to N-BSI,women with M-BSI had greater increase with exertion in VALR(-1.8%vs.6.1%,p=0.01)and VILR(1.5%vs.4.8%,p=0.03).Similarly,compared to N-BSI,vertical stiffness increased more with exertion among women with M-BSI(-0.9%vs.7.3%,p=0.006)and 1-BSI(-0.9%vs.1.8%,p=0.05).Finally,compared to N-BSI,the increase in tibial shock from fresh to exerted condition was greater among women with M-BSI(0.9%vs.5.5%,p=0.03)and 1-BSI(0.9%vs.11.2%,p=0.02).Conclusion:Women with 1-BSI or M-BSIs experience greater exertion-related increases in impact loading than women with N-BSI.These observations imply that exertion-related changes in gait biomechanics may contribute to risk of BSI.展开更多
Objective: To investigate the effects of Panax notoginseng saponins (PNS) on hydrogen peroxide (H2O2)-induced apoptosis in cultured rabbit bone marrow stromal cells (BMSCs). Methods: The effects of different c...Objective: To investigate the effects of Panax notoginseng saponins (PNS) on hydrogen peroxide (H2O2)-induced apoptosis in cultured rabbit bone marrow stromal cells (BMSCs). Methods: The effects of different concentrations of PNS on proliferation and early osteoblast differentiation of BMSCs were determined by the MTT assay and an alkaline phosphatase (ALP) assay. An optimal effective concentration of PNS was determined and used in subsequent experiments. The cultured BMSCs were divided into three groups: untreated control, H2O2 treated, and PNS pretreatment of H2O2 treated. The oxidative stress level was assessed by superoxide dismutase (SOD) and malondialdehyde (MDA) assays. Flow cytometry was used to determine BMSC apoptosis by staining with annexinV-FITC/propidium iodide (PI). The activity of caspase-3 enzyme was measured by spectrofluorometry. Results: PNS (0.1g/L) significantly increased both BMSC proliferation rate and ALP activity, while it decreased the indicators of oxidative stress, caspase-3 activity, and the apoptosis rate of BMSCs induced by H2O2.. Conclusion: PNS, acting as a biological antioxidant, had a protective effect on H2O2-induced apoptosis in cultured rabbit BMSCs by decreasing oxidative stress and down-regulating caspase-3.展开更多
AIM:To explore ex vivo the role of bone morphogenetic protein-4(BMP-4) and transforming growth factorbeta1(TGF-β1) in acute valvular response to fluid shear stress(FSS) abnormalities.METHODS:Porcine valve leaflets we...AIM:To explore ex vivo the role of bone morphogenetic protein-4(BMP-4) and transforming growth factorbeta1(TGF-β1) in acute valvular response to fluid shear stress(FSS) abnormalities.METHODS:Porcine valve leaflets were subjected ex vivo to physiologic FSS,supra-physiologic FSS magnitude at normal frequency and supra-physiologic FSS frequency at normal magnitude for 48 h in a double-sided cone-and-plate bioreactor filled with standard culture medium. The role of BMP-4 and TGF-β1 in the valvular response was investigated by promoting or inhibiting the downstream action of those cytokines via culture medium supplementation with BMP-4 or the BMP antagonist noggin,and TGF-β1 or the TGF-β1 inhibitor SB-431542,respectively. Fresh porcine leaflets were used as controls. Each experimental group consisted of six leaflet samples. Immunostaining and immunoblotting were performed to assess endothelial activation in terms of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expressions,paracrine signaling in terms of BMP-4 and TGF-β1 expressions and extracellular matrix(ECM) remodeling in terms of cathepsin L,cathepsin S,metalloproteinases(MMP)-2 and MMP-9 expressions. Immunostained images were quantified by normalizing the intensities of positively stained regions by the number of cells in each image while immunoblots were quantified by densitometry. R E S U LT S :Regardless of the culture medium,physiologic FSS maintained valvular homeostasis. Tissue exposure to supra-physiologic FSS magnitude in standard medium stimulated paracrine signaling(TGF-β1:467% ± 22% vs 100% ± 6% in freshcontrols,BMP-4:258% ± 22% vs 100% ± 4% in fresh controls; P < 0.05) and ECM degradation(MMP-2:941% ± 90% vs 100% ± 19% in fresh controls,MMP-9:1219% ± 190% vs 100% ± 16% in fresh controls,cathepsin L:1187% ± 175% vs 100% ± 12% in fresh controls,cathepsin S:603% ± 88% vs 100% ± 13% in fresh controls; P < 0.05),while BMP-4 supplementation also promoted fibrosa activation and TGF-β1 inhibition reduced MMP-9 expression to the native tissue level(MMP-9:308% ± 153% with TGF-β1 inhibition vs 100% ± 16% in fresh control; P > 0.05). Supra-physiologic FSS frequency had no effect on endothelial activation and paracrine signaling regardless of the culture medium but TGF-β1 silencing attenuated FSS-induced ECM degradation via MMP-9 downregulation(MMP-9:302% ± 182% vs 100% ± 42% in fresh controls; P > 0.05).CONCLUSION:Valvular tissue is sensitive to FSS abnormalities. The TGF-β1 inhibitor SB-431542 is a potential candidate molecule for attenuating the effects of FSS abnormalities on valvular remodeling.展开更多
This imaginary transformation from Sméagol to Gollum is a dramatization of the illusive repercussions of mechanical stress affecting bone. This paper presents the main ideas of mechanical stress and bone remodell...This imaginary transformation from Sméagol to Gollum is a dramatization of the illusive repercussions of mechanical stress affecting bone. This paper presents the main ideas of mechanical stress and bone remodelling from a novel’s perspective. The object of this study is to provide evidence for new ways to explore bone’s functional adaptation to mechanical stress made through the copious interpretation and integration of new and existing literature. It tackles the underlying biology of bone cells and how they detect and react to strain stimuli. The different types of mechanical demands in daily activities are sifted through and any misconceptions found fallible in literature are refined. A personal experience of a stress fracture is reviewed to parallel the implications that lead to the incident with the findings on the link between mechanical stress and bone remodelling. Some factors regarding age, gender and ethnicity and the interplay with mechanical stress influencing bone remodelling are considered. Brief overviews of three new medical novelties in bone healing are outlined, hoping that these interventions of proper medical techniques can be a change for the better: one from Gollum to Sméagol rather than vice versa.展开更多
The objective of this study was to study the age-related adaptation of lumbar vertebral trabecular bone at the apparent level, as well as the tissue level in three orthogonal directions. Ninety trabecular specimens we...The objective of this study was to study the age-related adaptation of lumbar vertebral trabecular bone at the apparent level, as well as the tissue level in three orthogonal directions. Ninety trabecular specimens were obtained from six normal L4 vertebral bodies of six male cadavers in two age groups, three aged 62 years and three aged 69 years, and were scanned using a high-resolution micro-computed tomography (micro-CT) system, then converted to micro- finite element models to do micro-finite element analyses. The relationship between apparent stiffness and bone volume fraction, and the tissue level yon Mises stress distribution for each trabecular specimen when compressed separately in the longitudinal direction, medial-lateral and anterior-posterior directions (transverse directions) were derived and compared between two age groups. The results showed that at the apparent level, trabecular bones from 69-year group had stiffer bone structure relative to their volume fractions in all three directions, and in both age groups, changes in bone volume fraction could explain more variations in apparent stiffness in the longitudinal direction than the transverse directions; at the tissue level, aging had little effect on the tissue von Mises stress distributions for the compressions in all the three directions. The novelty of the present study was that it provided quantitative assessments on the age and direction- related adaptation of Chinese male lumbar vertebral trabecular bone from two different levels: stiffness at the apparent level and stress distribution at the tissue level. It may help to understand the failure mechanisms and fracture risks of vertebral body associated with aging and direction for the prevention of fracture risks in elder individuals.展开更多
The present study aims to evaluate the effect of bone marrow mesenchymal stem cells on cold stress induced neuronal changes in hippocampal CA1 region of Wistar rats. Bone marrow mes- enchymal stem cells were isolated ...The present study aims to evaluate the effect of bone marrow mesenchymal stem cells on cold stress induced neuronal changes in hippocampal CA1 region of Wistar rats. Bone marrow mes- enchymal stem cells were isolated from a 6-week-old Wistar rat. Bone marrow from adult femora and tibia was collected and mesenchymal stem cells were cultured in minimal essential medium containing 10% heat-inactivated fetal bovine serum and were sub-cultured. Passage 3 cells were analyzed by flow cytometry for positive expression of CD44 and CD90 and negative expression of CD45. Once CD44 and CD90 positive expression was achieved, the cells were cultured again to 90% confluence for later experiments. Twenty-four rats aged 8 weeks old were randomly and evenly divided into normal control, cold water swim stress (cold stress), cold stress + PBS (intra- venous infusion), and cold stress + bone marrow mesenchymal stem cells (1 x 106; intravenous infusion) groups. The total period of study was 60 days which included 1 month stress period followed by 1 month treatment. Behavioral functional test was performed during the entire study period. After treatment, rats were sacrificed for histological studies. Treatment with bone marrow mesenchymal stem cells significantly increased the number of neuronal cells in hippocampal CA 1 region. Adult bone marrow mesenchymal stem cells injected by intravenous administration show potential therapeutic effects in cognitive decline associated with stress-related lesions.展开更多
背景:有研究利用三维有限元方法分析了种植体在不同皮质骨厚度中的应力情况,得出皮质骨厚度影响种植体-骨界面位移值、等效应力值及种植体各部件等效应力值的结果。目前超短种植体在不同下颌骨骨质中的临床应用还存在不确定性。目的:利...背景:有研究利用三维有限元方法分析了种植体在不同皮质骨厚度中的应力情况,得出皮质骨厚度影响种植体-骨界面位移值、等效应力值及种植体各部件等效应力值的结果。目前超短种植体在不同下颌骨骨质中的临床应用还存在不确定性。目的:利用三维有限元法分析超短种植体在下颌骨不同骨质中的应力分布及骨组织的应力分布情况。方法:选取1名下颌第1磨牙缺失患者的CT影像资料,利用Mimics软件创建下颌骨第1磨牙区域的模型,根据超短种植体奥齿泰系统中5 mm×5 mm TSⅢ型号绘制出所需要的植体及上部修复体模型,使用Geomagic Studio的偏置命令获取下颌4类不同骨质的模型(Ⅰ、Ⅱ、Ⅲ、Ⅳ类),将所有模型整合并交叉组合,给予不同方向载荷,分析各类模型受力后的范氏等效应力分布。结果与结论:(1)垂直载荷时:皮质骨最大应力在Ⅰ、Ⅱ、Ⅲ类骨质中相对于Ⅳ类骨更趋向于稳定,力也从分散于种植体周围到Ⅳ类骨时逐渐集中至种植体颈部与皮质骨连接处;Ⅰ类骨中最大等效应力峰值在中央螺丝区域,Ⅱ、Ⅲ、Ⅳ类骨中最大应力峰值则统一在种植体颈部与基台连接处。(2)侧向载荷时:皮质骨最大应力随着骨质条件的减弱呈逐渐增大的趋势;Ⅰ-Ⅳ类骨质中,最大应力峰值都集中在种植体与基台连接处,Ⅰ-Ⅲ类骨中种植体本身所受应力随着骨质的减弱表现出逐渐增大的趋势,到Ⅳ类骨时应力有所减小,此规律同样适用于修复体基台以及松质骨所受应力。(3)各类骨质中侧向载荷时所受到的最大应力值比垂直向载荷更大。展开更多
Background:Tibial stress fracture(TSF)is an overuse running injury with a long recovery period.While many running studies refer to biomechanical risk factors for TSF,only a few have compared biomechanics in runners wi...Background:Tibial stress fracture(TSF)is an overuse running injury with a long recovery period.While many running studies refer to biomechanical risk factors for TSF,only a few have compared biomechanics in runners with TSF to controls.The aim of this systematic review and meta-analysis was to evaluate biomechanics in runners with TSF compared to controls.Methods:Electronic databases PubMed,Web of Science,SPORTDiscus,Scopus,Cochrane,and CINAHL were searched.Risk of bias was assessed and meta-analysis conducted for variables reported in 3 or more studies.Results:The search retrieved 359 unique records,but only the 14 that compared runners with TSF to controls were included in the review.Most studies were retrospective,2 were prospective,and most had a small sample size(5-30 per group).Many variables were not significantly different between groups.Meta-analysis of peak impact,active,and braking ground reaction forces found no significant differences between groups.Individual studies found larger tibial peak anterior tensile stress,peak posterior compressive stress,peak axial acceleration,peak rearfoot eversion,and hip adduction in the TSF group.Conclusion:Meta-analysis indicated that discrete ground reaction force variables were not statistically significantly different in runners with TSF compared to controls.In individual included studies,many biomechanical variables were not statistically significantly different between groups.However,many were reported by only a single study,and sample sizes were small.We encourage additional studies with larger sample sizes of runners with TSF and controls and adequate statistical power to confirm or refute these findings.展开更多
背景:常见的退行性骨骼疾病,如骨关节炎、骨质疏松症和椎间盘退变,其具体的发病分子机制目前尚未明确,可能涉及内质网应激。目前,关于内质网应激在这些常见骨骼疾病发病机制中的系统作用和相关治疗进展的研究较为有限。目的:综述内质网...背景:常见的退行性骨骼疾病,如骨关节炎、骨质疏松症和椎间盘退变,其具体的发病分子机制目前尚未明确,可能涉及内质网应激。目前,关于内质网应激在这些常见骨骼疾病发病机制中的系统作用和相关治疗进展的研究较为有限。目的:综述内质网应激在常见的退行性骨骼疾病中的作用,深入探讨这些疾病的分子机制并提供新的防治思路和视角。方法:检索2000-2024年相关文献,以“内质网应激,骨骼疾病,未折叠蛋白反应,骨关节炎,骨质疏松症,椎间盘退变,自噬,凋亡,铁死亡,焦亡”为中文检索词检索中国知网、万方、维普数据库;以“endoplasmic reticulum stress,bone disease,unfolded protein response,osteoarthritis,osteoporosis,intervertebral disc degeneration,autophagy,apoptosis,ferroptosis,pyroptosis”为英文检索词检索PubMed、Web of Science数据库。排除重复和较陈旧的文献,共115篇文献符合纳入标准。结果与结论:①内质网应激在细胞生理调节中具有双重效应。轻度的内质网应激有助于促进成骨分化和细胞外基质合成,然而持续过度的内质网应激则会导致细胞死亡。②内质网应激诱导的细胞自噬、凋亡等与骨关节炎、骨质疏松症、椎间盘退变密切相关。③衰老、药物不良反应、代谢紊乱、钙平衡失调、不良生活习惯等多种原因可导致内质网应激的长期激活,从而引起骨重塑紊乱、软骨损伤、髓核细胞死亡等病理表现,最终导致骨关节炎、骨质疏松和椎间盘退变的发生。④对引发内质网应激的相关机制进行干预,有望在预防和治疗骨关节炎、骨质疏松症和椎间盘退变等常见退行性骨病方面发挥作用。展开更多
Granulopoiesis in murine bone-marrow is regulated by both intrinsic and extrinsic factors(including hormones, drugs, inflammatory mediators and cytokines). Eosinophils, a minor subpopulation of circulating leukocytes,...Granulopoiesis in murine bone-marrow is regulated by both intrinsic and extrinsic factors(including hormones, drugs, inflammatory mediators and cytokines). Eosinophils, a minor subpopulation of circulating leukocytes, which remains better understood in its contributions to tissue injury in allergic disease than in its presumably beneficial actions in host defense, provide a striking example of joint regulation of granulopoiesis within murine bone-marrow by all of these classes of extrinsic factors. We first described the upregulation of eosinopoiesis in bone-marrow of allergen-sensitized mice following airway allergen challenge. Over the last decade, we were able to show a critical role for endogenous glucocorticoid hormones and cytokines in mediating this phenomenon through modification of cytokine effects, thereby supporting a positive association between stress hormones and allergic reactions. We have further shown that cysteinylleukotrienes(Cys LT), a major proinflammatory class of lipid mediators, generated through the 5-lipoxygenase pathway, upregulate bone-marrow eosinopoiesis in vivo and in vitro. Cys LT mediate the positive effects of drugs(indomethacin and aspirin) and of proallergic cytokines(eotaxin/CCL11 and interleukin-13) on in vitro eosinopoiesis. While these actions of endogenous GC and Cys LT might seem unrelated and even antagonistic, we demonstrated a critical partnership of these mediators in vivo, shedding light on mechanisms linking stress to allergy: GC are required for Cys LT-mediated upregulation of bone-marrow eosinopoiesis in vivo, but also attenuate subsequent ex vivo responses to Cys LT. GC and Cys LT therefore work together to induce eosinophilia, but through subtle regulatory mechanisms also limit the magnitude of subsequent bone-marrow responses to allergen.展开更多
Stress fracture(SF)in military recruits in China was investigated using<sup>99m</sup>Tc-MDP bone scintigraphy in a randomized sample of 432 injured who wereclinically screened from 1060 recruits during b...Stress fracture(SF)in military recruits in China was investigated using<sup>99m</sup>Tc-MDP bone scintigraphy in a randomized sample of 432 injured who wereclinically screened from 1060 recruits during basic training.The relationship between SFand training intensity was discussed.It was shown that the total incidence was 32.5%.There were two peaks during 9 training-weeks:one was in the 2nd week,and the otherin the 7th.Infantry soldiers had a more intensive training and,therefore a higher inci-dence than in artillery and service troops.Although SF was found in most ofweight-bearing bones,tibia was most commonly fractured(67%).The findings suggestthat SF is a major training-related injury in military recruits and improperly strengthenedtraining can increase the incidence.展开更多
Athletes and military recruits are often afflicted by stress fractures. Rigorous training programs consisting of increased repetitive mechanical loading may contribute to the high incidence of tibia stress fracture in...Athletes and military recruits are often afflicted by stress fractures. Rigorous training programs consisting of increased repetitive mechanical loading may contribute to the high incidence of tibia stress fracture in the athletic and army populations. The purpose of this study was to assess the effect of incremented height on tibia bone strains and strain rates during landing. Seven healthy college males performed drop-landing tasks from 26 cm, 39 cm, and 52 cm, respectively. Tibia bone strains and strain rates were obtained through subject-specific multi-body dynamic computer simulations and finite element analyses. One-way repeated measures ANOVAs were conducted. Both 39 cm and 52 cm conditions resulted in larger tibia bone strains and strain rates than the 26 cm condition. The 52 cm condition also resulted in greater bone strains and strain rates than the 39 cm condition. A dose-response relationship exists between incremented landing height and bone strains and strain rates. Activities consisting of high impact landings are associated with increased risk of developing tibia stress fracture. When designing training programs involved high impact activities, athletes and military recruits should consider the effect of impact loading on tibia bone health and giving enough time for bones to adapt to new trainings.展开更多
Polymethylmethacrylate (PMMA) bone cement is a polymeric material that is widely used as a structural orthopedic material. However, it is not an ideal material for bone grafting due to its fragility. Carbon nanotubes ...Polymethylmethacrylate (PMMA) bone cement is a polymeric material that is widely used as a structural orthopedic material. However, it is not an ideal material for bone grafting due to its fragility. Carbon nanotubes (CNTs) have been introduced in order to reinforce PMMA resulting in a composite material which exhibits improved tensile properties, increased fatigue resistance and fracture toughness. This improvement is potentially due to bridging and arresting cracks as well as absorption of energy. In this study, a two-dimensional finite element model is presented for the fracture analysis of PMMA-CNT composite material. Instead of the classical single fiber model, the present work considers an ensemble of CNTs interacting with a pre-existing crack. Casca is used to produce a two dimensional mesh and the fracture analysis is performed using Franc 2D. The model is subjected to uni-axial loading in the transverse plane and the interaction between the crack and CNTs is evaluated by determining the stress intensity factor in the vicinity of the crack tips. The effects of geometric parameters of the CNTs and the material structural heterogeneity on crack propagation trajectory are investigated. Furthermore, the effects of CNT diameter, wall thickness and elastic mismatch between the matrix and the nanotubes on crack growth are studied. The results illustrate that the CNTs repel cracks during loading as they act as barriers to crack growth. As a result, the incorporation of CNTs into PMMA reduces crack growth but more importantly increases the fracture resistance of bone cement.展开更多
基金supported in part by appointments to the Department of Defense Research Participation Program at the U.S.Army Research Institute of Environmental Medicine administered by the Oak Ridge Institute for Science and Educationsupport from the U.S.Department of Defense+2 种基金Defense Health ProgramJoint Program Committee(W81XWH-16-1-0652)the National Institutes of Health shared instrumentation grant(S10 RR023405)。
文摘Background:Bone stress injuries(BSIs)are common in female runners,and recurrent BSI rates are high.Previous work suggests an association between higher impact loading during running and tibial BSI.However,it is unknown whether impact loading and fatigue-related loading changes discriminate women with a history of multiple BSIs.This study compared impact variables at the beginning of a treadmill run to exertion andthe changes in those variables with exertion among female runners with no history of BSI as well as among those with a history of single or multiple BSIs.Methods:We enrolled 45 female runners(aged 18-40 years)for this cross-sectional study:having no history of diagnosed lower extremity BSI(N-BSI,n=14);a history of 1 lower extremity BSI(1-BSI,n=16);and diagnosed by imaging,or a history of multiple(>3)lower extremity BSIs(M-BSI,n=15).Participants completed a 5-km race speed run on an instrumented treadmill while wearing an Inertial Measurement Unit.The vertical average loading rate(VALR),vertical instantaneous loading rate(VILR),vertical stiffness during impact via instrumented treadmill,and tibial shock determined as the peak po sitive tibial acceleration via Inertial Measurement Unit were measured at the beginning and the end of the run.Results:There were no differences between groups in VALR,VILR,vertical stiffness,or tibial shock in a fresh or exerted condition.However,compared to N-BSI,women with M-BSI had greater increase with exertion in VALR(-1.8%vs.6.1%,p=0.01)and VILR(1.5%vs.4.8%,p=0.03).Similarly,compared to N-BSI,vertical stiffness increased more with exertion among women with M-BSI(-0.9%vs.7.3%,p=0.006)and 1-BSI(-0.9%vs.1.8%,p=0.05).Finally,compared to N-BSI,the increase in tibial shock from fresh to exerted condition was greater among women with M-BSI(0.9%vs.5.5%,p=0.03)and 1-BSI(0.9%vs.11.2%,p=0.02).Conclusion:Women with 1-BSI or M-BSIs experience greater exertion-related increases in impact loading than women with N-BSI.These observations imply that exertion-related changes in gait biomechanics may contribute to risk of BSI.
基金supported by National Natural Science Foundation of China (30600624)
文摘Objective: To investigate the effects of Panax notoginseng saponins (PNS) on hydrogen peroxide (H2O2)-induced apoptosis in cultured rabbit bone marrow stromal cells (BMSCs). Methods: The effects of different concentrations of PNS on proliferation and early osteoblast differentiation of BMSCs were determined by the MTT assay and an alkaline phosphatase (ALP) assay. An optimal effective concentration of PNS was determined and used in subsequent experiments. The cultured BMSCs were divided into three groups: untreated control, H2O2 treated, and PNS pretreatment of H2O2 treated. The oxidative stress level was assessed by superoxide dismutase (SOD) and malondialdehyde (MDA) assays. Flow cytometry was used to determine BMSC apoptosis by staining with annexinV-FITC/propidium iodide (PI). The activity of caspase-3 enzyme was measured by spectrofluorometry. Results: PNS (0.1g/L) significantly increased both BMSC proliferation rate and ALP activity, while it decreased the indicators of oxidative stress, caspase-3 activity, and the apoptosis rate of BMSCs induced by H2O2.. Conclusion: PNS, acting as a biological antioxidant, had a protective effect on H2O2-induced apoptosis in cultured rabbit BMSCs by decreasing oxidative stress and down-regulating caspase-3.
基金Supported by American Heart Association Scientist Development Grant,No.11SDG7600103
文摘AIM:To explore ex vivo the role of bone morphogenetic protein-4(BMP-4) and transforming growth factorbeta1(TGF-β1) in acute valvular response to fluid shear stress(FSS) abnormalities.METHODS:Porcine valve leaflets were subjected ex vivo to physiologic FSS,supra-physiologic FSS magnitude at normal frequency and supra-physiologic FSS frequency at normal magnitude for 48 h in a double-sided cone-and-plate bioreactor filled with standard culture medium. The role of BMP-4 and TGF-β1 in the valvular response was investigated by promoting or inhibiting the downstream action of those cytokines via culture medium supplementation with BMP-4 or the BMP antagonist noggin,and TGF-β1 or the TGF-β1 inhibitor SB-431542,respectively. Fresh porcine leaflets were used as controls. Each experimental group consisted of six leaflet samples. Immunostaining and immunoblotting were performed to assess endothelial activation in terms of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expressions,paracrine signaling in terms of BMP-4 and TGF-β1 expressions and extracellular matrix(ECM) remodeling in terms of cathepsin L,cathepsin S,metalloproteinases(MMP)-2 and MMP-9 expressions. Immunostained images were quantified by normalizing the intensities of positively stained regions by the number of cells in each image while immunoblots were quantified by densitometry. R E S U LT S :Regardless of the culture medium,physiologic FSS maintained valvular homeostasis. Tissue exposure to supra-physiologic FSS magnitude in standard medium stimulated paracrine signaling(TGF-β1:467% ± 22% vs 100% ± 6% in freshcontrols,BMP-4:258% ± 22% vs 100% ± 4% in fresh controls; P < 0.05) and ECM degradation(MMP-2:941% ± 90% vs 100% ± 19% in fresh controls,MMP-9:1219% ± 190% vs 100% ± 16% in fresh controls,cathepsin L:1187% ± 175% vs 100% ± 12% in fresh controls,cathepsin S:603% ± 88% vs 100% ± 13% in fresh controls; P < 0.05),while BMP-4 supplementation also promoted fibrosa activation and TGF-β1 inhibition reduced MMP-9 expression to the native tissue level(MMP-9:308% ± 153% with TGF-β1 inhibition vs 100% ± 16% in fresh control; P > 0.05). Supra-physiologic FSS frequency had no effect on endothelial activation and paracrine signaling regardless of the culture medium but TGF-β1 silencing attenuated FSS-induced ECM degradation via MMP-9 downregulation(MMP-9:302% ± 182% vs 100% ± 42% in fresh controls; P > 0.05).CONCLUSION:Valvular tissue is sensitive to FSS abnormalities. The TGF-β1 inhibitor SB-431542 is a potential candidate molecule for attenuating the effects of FSS abnormalities on valvular remodeling.
文摘This imaginary transformation from Sméagol to Gollum is a dramatization of the illusive repercussions of mechanical stress affecting bone. This paper presents the main ideas of mechanical stress and bone remodelling from a novel’s perspective. The object of this study is to provide evidence for new ways to explore bone’s functional adaptation to mechanical stress made through the copious interpretation and integration of new and existing literature. It tackles the underlying biology of bone cells and how they detect and react to strain stimuli. The different types of mechanical demands in daily activities are sifted through and any misconceptions found fallible in literature are refined. A personal experience of a stress fracture is reviewed to parallel the implications that lead to the incident with the findings on the link between mechanical stress and bone remodelling. Some factors regarding age, gender and ethnicity and the interplay with mechanical stress influencing bone remodelling are considered. Brief overviews of three new medical novelties in bone healing are outlined, hoping that these interventions of proper medical techniques can be a change for the better: one from Gollum to Sméagol rather than vice versa.
基金The project supported by the Hong Kong Polytechnic University Research Grants(G-U273) the National Natural Science Foundation of China(10502021 and 10529202)
文摘The objective of this study was to study the age-related adaptation of lumbar vertebral trabecular bone at the apparent level, as well as the tissue level in three orthogonal directions. Ninety trabecular specimens were obtained from six normal L4 vertebral bodies of six male cadavers in two age groups, three aged 62 years and three aged 69 years, and were scanned using a high-resolution micro-computed tomography (micro-CT) system, then converted to micro- finite element models to do micro-finite element analyses. The relationship between apparent stiffness and bone volume fraction, and the tissue level yon Mises stress distribution for each trabecular specimen when compressed separately in the longitudinal direction, medial-lateral and anterior-posterior directions (transverse directions) were derived and compared between two age groups. The results showed that at the apparent level, trabecular bones from 69-year group had stiffer bone structure relative to their volume fractions in all three directions, and in both age groups, changes in bone volume fraction could explain more variations in apparent stiffness in the longitudinal direction than the transverse directions; at the tissue level, aging had little effect on the tissue von Mises stress distributions for the compressions in all the three directions. The novelty of the present study was that it provided quantitative assessments on the age and direction- related adaptation of Chinese male lumbar vertebral trabecular bone from two different levels: stiffness at the apparent level and stress distribution at the tissue level. It may help to understand the failure mechanisms and fracture risks of vertebral body associated with aging and direction for the prevention of fracture risks in elder individuals.
文摘The present study aims to evaluate the effect of bone marrow mesenchymal stem cells on cold stress induced neuronal changes in hippocampal CA1 region of Wistar rats. Bone marrow mes- enchymal stem cells were isolated from a 6-week-old Wistar rat. Bone marrow from adult femora and tibia was collected and mesenchymal stem cells were cultured in minimal essential medium containing 10% heat-inactivated fetal bovine serum and were sub-cultured. Passage 3 cells were analyzed by flow cytometry for positive expression of CD44 and CD90 and negative expression of CD45. Once CD44 and CD90 positive expression was achieved, the cells were cultured again to 90% confluence for later experiments. Twenty-four rats aged 8 weeks old were randomly and evenly divided into normal control, cold water swim stress (cold stress), cold stress + PBS (intra- venous infusion), and cold stress + bone marrow mesenchymal stem cells (1 x 106; intravenous infusion) groups. The total period of study was 60 days which included 1 month stress period followed by 1 month treatment. Behavioral functional test was performed during the entire study period. After treatment, rats were sacrificed for histological studies. Treatment with bone marrow mesenchymal stem cells significantly increased the number of neuronal cells in hippocampal CA 1 region. Adult bone marrow mesenchymal stem cells injected by intravenous administration show potential therapeutic effects in cognitive decline associated with stress-related lesions.
文摘背景:有研究利用三维有限元方法分析了种植体在不同皮质骨厚度中的应力情况,得出皮质骨厚度影响种植体-骨界面位移值、等效应力值及种植体各部件等效应力值的结果。目前超短种植体在不同下颌骨骨质中的临床应用还存在不确定性。目的:利用三维有限元法分析超短种植体在下颌骨不同骨质中的应力分布及骨组织的应力分布情况。方法:选取1名下颌第1磨牙缺失患者的CT影像资料,利用Mimics软件创建下颌骨第1磨牙区域的模型,根据超短种植体奥齿泰系统中5 mm×5 mm TSⅢ型号绘制出所需要的植体及上部修复体模型,使用Geomagic Studio的偏置命令获取下颌4类不同骨质的模型(Ⅰ、Ⅱ、Ⅲ、Ⅳ类),将所有模型整合并交叉组合,给予不同方向载荷,分析各类模型受力后的范氏等效应力分布。结果与结论:(1)垂直载荷时:皮质骨最大应力在Ⅰ、Ⅱ、Ⅲ类骨质中相对于Ⅳ类骨更趋向于稳定,力也从分散于种植体周围到Ⅳ类骨时逐渐集中至种植体颈部与皮质骨连接处;Ⅰ类骨中最大等效应力峰值在中央螺丝区域,Ⅱ、Ⅲ、Ⅳ类骨中最大应力峰值则统一在种植体颈部与基台连接处。(2)侧向载荷时:皮质骨最大应力随着骨质条件的减弱呈逐渐增大的趋势;Ⅰ-Ⅳ类骨质中,最大应力峰值都集中在种植体与基台连接处,Ⅰ-Ⅲ类骨中种植体本身所受应力随着骨质的减弱表现出逐渐增大的趋势,到Ⅳ类骨时应力有所减小,此规律同样适用于修复体基台以及松质骨所受应力。(3)各类骨质中侧向载荷时所受到的最大应力值比垂直向载荷更大。
文摘Background:Tibial stress fracture(TSF)is an overuse running injury with a long recovery period.While many running studies refer to biomechanical risk factors for TSF,only a few have compared biomechanics in runners with TSF to controls.The aim of this systematic review and meta-analysis was to evaluate biomechanics in runners with TSF compared to controls.Methods:Electronic databases PubMed,Web of Science,SPORTDiscus,Scopus,Cochrane,and CINAHL were searched.Risk of bias was assessed and meta-analysis conducted for variables reported in 3 or more studies.Results:The search retrieved 359 unique records,but only the 14 that compared runners with TSF to controls were included in the review.Most studies were retrospective,2 were prospective,and most had a small sample size(5-30 per group).Many variables were not significantly different between groups.Meta-analysis of peak impact,active,and braking ground reaction forces found no significant differences between groups.Individual studies found larger tibial peak anterior tensile stress,peak posterior compressive stress,peak axial acceleration,peak rearfoot eversion,and hip adduction in the TSF group.Conclusion:Meta-analysis indicated that discrete ground reaction force variables were not statistically significantly different in runners with TSF compared to controls.In individual included studies,many biomechanical variables were not statistically significantly different between groups.However,many were reported by only a single study,and sample sizes were small.We encourage additional studies with larger sample sizes of runners with TSF and controls and adequate statistical power to confirm or refute these findings.
文摘背景:常见的退行性骨骼疾病,如骨关节炎、骨质疏松症和椎间盘退变,其具体的发病分子机制目前尚未明确,可能涉及内质网应激。目前,关于内质网应激在这些常见骨骼疾病发病机制中的系统作用和相关治疗进展的研究较为有限。目的:综述内质网应激在常见的退行性骨骼疾病中的作用,深入探讨这些疾病的分子机制并提供新的防治思路和视角。方法:检索2000-2024年相关文献,以“内质网应激,骨骼疾病,未折叠蛋白反应,骨关节炎,骨质疏松症,椎间盘退变,自噬,凋亡,铁死亡,焦亡”为中文检索词检索中国知网、万方、维普数据库;以“endoplasmic reticulum stress,bone disease,unfolded protein response,osteoarthritis,osteoporosis,intervertebral disc degeneration,autophagy,apoptosis,ferroptosis,pyroptosis”为英文检索词检索PubMed、Web of Science数据库。排除重复和较陈旧的文献,共115篇文献符合纳入标准。结果与结论:①内质网应激在细胞生理调节中具有双重效应。轻度的内质网应激有助于促进成骨分化和细胞外基质合成,然而持续过度的内质网应激则会导致细胞死亡。②内质网应激诱导的细胞自噬、凋亡等与骨关节炎、骨质疏松症、椎间盘退变密切相关。③衰老、药物不良反应、代谢紊乱、钙平衡失调、不良生活习惯等多种原因可导致内质网应激的长期激活,从而引起骨重塑紊乱、软骨损伤、髓核细胞死亡等病理表现,最终导致骨关节炎、骨质疏松和椎间盘退变的发生。④对引发内质网应激的相关机制进行干预,有望在预防和治疗骨关节炎、骨质疏松症和椎间盘退变等常见退行性骨病方面发挥作用。
文摘Granulopoiesis in murine bone-marrow is regulated by both intrinsic and extrinsic factors(including hormones, drugs, inflammatory mediators and cytokines). Eosinophils, a minor subpopulation of circulating leukocytes, which remains better understood in its contributions to tissue injury in allergic disease than in its presumably beneficial actions in host defense, provide a striking example of joint regulation of granulopoiesis within murine bone-marrow by all of these classes of extrinsic factors. We first described the upregulation of eosinopoiesis in bone-marrow of allergen-sensitized mice following airway allergen challenge. Over the last decade, we were able to show a critical role for endogenous glucocorticoid hormones and cytokines in mediating this phenomenon through modification of cytokine effects, thereby supporting a positive association between stress hormones and allergic reactions. We have further shown that cysteinylleukotrienes(Cys LT), a major proinflammatory class of lipid mediators, generated through the 5-lipoxygenase pathway, upregulate bone-marrow eosinopoiesis in vivo and in vitro. Cys LT mediate the positive effects of drugs(indomethacin and aspirin) and of proallergic cytokines(eotaxin/CCL11 and interleukin-13) on in vitro eosinopoiesis. While these actions of endogenous GC and Cys LT might seem unrelated and even antagonistic, we demonstrated a critical partnership of these mediators in vivo, shedding light on mechanisms linking stress to allergy: GC are required for Cys LT-mediated upregulation of bone-marrow eosinopoiesis in vivo, but also attenuate subsequent ex vivo responses to Cys LT. GC and Cys LT therefore work together to induce eosinophilia, but through subtle regulatory mechanisms also limit the magnitude of subsequent bone-marrow responses to allergen.
文摘Stress fracture(SF)in military recruits in China was investigated using<sup>99m</sup>Tc-MDP bone scintigraphy in a randomized sample of 432 injured who wereclinically screened from 1060 recruits during basic training.The relationship between SFand training intensity was discussed.It was shown that the total incidence was 32.5%.There were two peaks during 9 training-weeks:one was in the 2nd week,and the otherin the 7th.Infantry soldiers had a more intensive training and,therefore a higher inci-dence than in artillery and service troops.Although SF was found in most ofweight-bearing bones,tibia was most commonly fractured(67%).The findings suggestthat SF is a major training-related injury in military recruits and improperly strengthenedtraining can increase the incidence.
文摘Athletes and military recruits are often afflicted by stress fractures. Rigorous training programs consisting of increased repetitive mechanical loading may contribute to the high incidence of tibia stress fracture in the athletic and army populations. The purpose of this study was to assess the effect of incremented height on tibia bone strains and strain rates during landing. Seven healthy college males performed drop-landing tasks from 26 cm, 39 cm, and 52 cm, respectively. Tibia bone strains and strain rates were obtained through subject-specific multi-body dynamic computer simulations and finite element analyses. One-way repeated measures ANOVAs were conducted. Both 39 cm and 52 cm conditions resulted in larger tibia bone strains and strain rates than the 26 cm condition. The 52 cm condition also resulted in greater bone strains and strain rates than the 39 cm condition. A dose-response relationship exists between incremented landing height and bone strains and strain rates. Activities consisting of high impact landings are associated with increased risk of developing tibia stress fracture. When designing training programs involved high impact activities, athletes and military recruits should consider the effect of impact loading on tibia bone health and giving enough time for bones to adapt to new trainings.
文摘Polymethylmethacrylate (PMMA) bone cement is a polymeric material that is widely used as a structural orthopedic material. However, it is not an ideal material for bone grafting due to its fragility. Carbon nanotubes (CNTs) have been introduced in order to reinforce PMMA resulting in a composite material which exhibits improved tensile properties, increased fatigue resistance and fracture toughness. This improvement is potentially due to bridging and arresting cracks as well as absorption of energy. In this study, a two-dimensional finite element model is presented for the fracture analysis of PMMA-CNT composite material. Instead of the classical single fiber model, the present work considers an ensemble of CNTs interacting with a pre-existing crack. Casca is used to produce a two dimensional mesh and the fracture analysis is performed using Franc 2D. The model is subjected to uni-axial loading in the transverse plane and the interaction between the crack and CNTs is evaluated by determining the stress intensity factor in the vicinity of the crack tips. The effects of geometric parameters of the CNTs and the material structural heterogeneity on crack propagation trajectory are investigated. Furthermore, the effects of CNT diameter, wall thickness and elastic mismatch between the matrix and the nanotubes on crack growth are studied. The results illustrate that the CNTs repel cracks during loading as they act as barriers to crack growth. As a result, the incorporation of CNTs into PMMA reduces crack growth but more importantly increases the fracture resistance of bone cement.