The relationship between the spine-pelvis-lower extremity sagittal parameters and disease-related molecules in serum and synovial fluid in patients with knee osteoarthritis

Objective:To study the relationship between spine-pelvis-lower extremities sagittal parameters and disease-related molecules in serum and synovial fluid in patients with knee osteoarthritis. Methods:A total of 65 patients diagnosed with knee osteoarthritis in Dongguan Tangxia Hospital between May 2013 and December 2016 were collected as OA group, and 70 patients with meniscus and cruciate ligament injury undergoing repair surgery during the same period were collected as the control group. Spine-pelvis-lower extremity sagittal parameters were measured by erect whole spine lateral radiographs. The serum was collected and inflammatory factor contents were measured. The synovial fluid was collected to determine inflammatory factor contents and apoptosis molecule expression.Results: Affected-side PFA and SFA levels of OA group were significantly lower than those of healthy side while FI and ST levels were significantly higher than those of healthy side;serum TNF-α, IL-1β, IL-18, MMP1 and MMP3 contents of OA group were significantly higher than those of control group, negatively correlated with PFA and SFA levels, and positively correlated with FI and ST levels;TNF-α, IL-1β, IL-18, MMP1, MMP3, Fas, FasL, Caveolin-1, NO, CHOP and GRP78 contents in synovial fluid of OA group were significantly higher than those of control group, negatively correlated with PFA and SFA levels, and positively correlated with FI and ST levels. Conclusion: Sagittal parameters of spine-pelvis-lower extremity can be used to evaluate the inflammatory response and apoptosis in patients with knee osteoarthritis.

Matrix stiffening promotes chondrocyte senescence and the osteoarthritis development through downregulating HDAC3

Extracellular matrix(ECM)stiffening is a typical characteristic of cartilage aging,which is a quintessential feature of knee osteoarthritis(KOA).However,little is known about how ECM stiffening affects chondrocytes and other molecules downstream.This study mimicked the physiological and pathological stiffness of human cartilage using polydimethylsiloxane(PDMS)substrates.It demonstrated that epigenetic Parkin regulation by histone deacetylase 3(HDAC3)represents a new mechanosensitive mechanism by which the stiffness matrix affected chondrocyte physiology.We found that ECM stiffening accelerated cultured chondrocyte senescence in vitro,while the stiffness ECM downregulated HDAC3,prompting Parkin acetylation to activate excessive mitophagy and accelerating chondrocyte senescence and osteoarthritis(OA)in mice.Contrarily,intra-articular injection with an HDAC3-expressing adeno-associated virus restored the young phenotype of the aged chondrocytes stimulated by ECM stiffening and alleviated OA in mice.The findings indicated that changes in the mechanical ECM properties initiated pathogenic mechanotransduction signals,promoted the Parkin acetylation and hyperactivated mitophagy,and damaged chondrocyte health.These results may provide new insights into chondrocyte regulation by the mechanical properties of ECM,suggesting that the modification of the physical ECM properties may be a potential OA treatment strategy.

Prevalence,Characteristics and Treatment of Knee Osteoarthritis in Urban Residents of Beijing,China:A Community-Based Cross-Sectional Study

Knee osteoarthritis(KOA)is a common progressive joint disease with chronic pain and movement disorders as the main clinical features.It is a major public health problem worldwide and it imposes serious medical and economic burdens.KOA accounts for nearly four-fifths of the global Osteoarthritis burden and increases with rising obesity and age[1].There are many reasons for the change in disease prevalence and risk factors,such as urbanization,lifestyle changes,population aging,and sex imbalances.

Targeted knockdown of PGAM5 in synovial macrophages efficiently alleviates osteoarthritis

Osteoarthritis(OA)is a common degenerative disease worldwide and new therapeutics that target inflammation and the crosstalk between immunocytes and chondrocytes are being developed to prevent and treat OA.These attempts involve repolarizing pro-inflammatory M1 macrophages into the anti-inflammatory M2 phenotype in synovium.In this study,we found that phosphoglycerate mutase 5(PGAM5)significantly increased in macrophages in OA synovium compared to controls based on histology of human samples and single-cell RNA sequencing results of mice models.To address the role of PGAM5 in macrophages in OA,we found conditional knockout of PGAM5 in macrophages greatly alleviated OA symptoms and promoted anabolic metabolism of chondrocytes in vitro and in vivo.Mechanistically,we found that PGAM5 enhanced M1 polarization via AKT-mTOR/p38/ERK pathways,whereas inhibited M2 polarization via STAT6-PPARγpathway in murine bone marrow-derived macrophages.Furthermore,we found that PGAM5 directly dephosphorylated Dishevelled Segment Polarity Protein 2(DVL2)which resulted in the inhibition ofβ-catenin and repolarization of M2 macrophages into M1 macrophages.Conditional knockout of both PGAM5 andβ-catenin in macrophages significantly exacerbated osteoarthritis compared to PGAM5-deficient mice.Motivated by these findings,we successfully designed mannose modified fluoropolymers combined with siPGAM5 to inhibit PGAM5 specifically in synovial macrophages via intra-articular injection,which possessed desired targeting abilities of synovial macrophages and greatly attenuated murine osteoarthritis.Collectively,these findings defined a key role for PGAM5 in orchestrating macrophage polarization and provides insights into novel macrophage-targeted strategy for treating OA.

Knee Osteoarthritis Progression after Distal Femur Closing Wedge Osteotomy

Background: Despite the conservative treatment of tibio-femoral osteoarthritis through realignment osteotomies, the rate of total knee replacements following an osteotomy is increasing. The aim of this study was to identify the factors associated with the progression of knee osteoarthritis after a medial closing-wedge distal femoral osteotomy. Methods: Hospital-based observational study on 20 patients who underwent a medial closing-wedge distal femoral osteotomy evaluating the progression of osteoarthritis using the Kellgren and Laurence classification. The Wilcoxon test was used to compare the variation in the progressive stage of the Kellgren and Laurence classification of knee osteoarthritis preoperatively and at the final follow up. Univariate analysis made it possible to determine the factors associated with progression. The final significance threshold for statistical tests was set at 5% (p Results: Overall, the mean follow-up of 46 months ± 6.6 months, with a mean age of 43 years (range: 27 - 69 years) and a female predominance (M: F = 3/7). The progression of tibiofemoral osteoarthritis following a medial closing-wedge distal femoral osteotomy is associated with valgus or varum malalignment been a moderate valgus (OR 6.2 [1.5 - 42.7] at 95% CI;p-value = 0.02), a correction of the mechanical deviation angle with a valgus alignment (OR 2.7 [0.9 - 8.3] at 95% CI), and loss of correction (OR 3.8 [1.3 - 11.6] at 95% CI;p -value) for the lateral compartment while varus alignment (OR 1.7 [0.9 - 8.3] 95% CI, p-value = 0.05) and with rupture of the lateral cortex (OR 2.8 [1.7 - 11.5] 95% CI, p-value = 0.02) were those of the medial compartment. Conclusion: Distal femur closing wedge osteotomy does not definitively interrupt the progression of valgus knee osteoarthritis. The factors associated with the progression of this pathology are modifiable. Taking them into account when performing this surgical technique could improve the osteotomy survival curve.

PCDH17 restricts dendritic spine morphogenesis by regulating ROCK2-dependent control of the actin cytoskeleton,modulating emotional behavior

Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain function.Synaptic abnormalities,such as defects in the density and morphology of postsynaptic dendritic spines,underlie the pathology of various neuropsychiatric disorders.Protocadherin 17(PCDH17)is associated with major mood disorders,including bipolar disorder and depression.However,the molecular mechanisms by which PCDH17 regulates spine number,morphology,and behavior remain elusive.In this study,we found that PCDH17 functions at postsynaptic sites,restricting the number and size of dendritic spines in excitatory neurons.Selective overexpression of PCDH17 in the ventral hippocampal CA1 results in spine loss and anxiety-and depression-like behaviors in mice.Mechanistically,PCDH17 interacts with actin-relevant proteins and regulates actin filament(F-actin)organization.Specifically,PCDH17 binds to ROCK2,increasing its expression and subsequently enhancing the activity of downstream targets such as LIMK1 and the phosphorylation of cofilin serine-3(Ser3).Inhibition of ROCK2 activity with belumosudil(KD025)ameliorates the defective F-actin organization and spine structure induced by PCDH17 overexpression,suggesting that ROCK2 mediates the effects of PCDH17 on F-actin content and spine development.Hence,these findings reveal a novel mechanism by which PCDH17 regulates synapse development and behavior,providing pathological insights into the neurobiological basis of mood disorders.

Epidemiological, Clinical and Paraclinical Profile of Osteoarthritis of the Lower Limbs in Obese Patients at the Cocody University Teaching Hospital

Objective: To describe the epidemiological, clinical and paraclinical characteristics of osteoarthritis of the lower limbs in obese patients at the Cocody University Teaching Hospital. Methodology: This was an analytical cross-sectional study carried out in the rheumatology department of the Cocody UTH in Abidjan (Ivory Coast) from March 1 to April 30 2023. Patients who came for rheumatology consultation presenting with mechanical arthralgia of the lower limbs, who were obese, had radiographic images were included. All patients without radiographic images were excluded. Obesity was defined as a body mass index (BMI) greater than or equal to 30 kg/m. The Chi2 test was used to compare proportions and determine the existence of associations between osteoarthristis and obesity, obesity severity and radiographic stage of osteoarthritis as well as the functional impact. A p-value below a predefined threshold (p = 0,05) indicates a significant relationship between the variables. Result: Out of 185 patients received for osteoarthritis of the lower limbs during the study period, 136 were obese (74%). There were 115 women (84.6%) with an average age of 56.03 with a standard deviation of 12.72 years (extremes: 22 and 84 years). The main socio-professional category was the informal sector (30%). The majority of patients had a low socio-economic level (80.2%) and lived in urban areas (92.6%). The most common past medical history was hypertension (33.08%) followed by peptic ulcer disease (16.91%). Patients had a body mass index class 1 (81.6%), class 2 (15.40%) and class 3 (2.90%). The average duration of symptom progression until diagnosis was 11 months. Genu varum was the main static disorder (56.10%) and the knee joint was the dominant topography (90.4%) with a bilateral localization (80%). The average Lequesne index was greater than 8 (59.5%). The Kellgren and Lawrence radiographic stages were stage 1 (9.20%), stage 2 (46.90%), stage 3 (29.20%) and stage 4 (6.90%). The Obesity severity was significantly associated with osteoarthritis of the knee (p = 0.042). There was no statistically significant association between obesity severity and radiographic stage of osteoarthritis (p = 0.163) or functional impact (p = 0.180). Conclusion: Osteoarthritis of the lower limbs affected obese women and was dominated by stage 2 osteoarthritis of the knee (Kellgren and Lawrence). There is an association between the severity of obesity and osteoarthritis of the knee.

Knee osteoarthritis:A review of animal models and intervention of traditional Chinese medicine

Background:Knee osteoarthritis(KOA)characterized by degeneration of knee cartilage and subsequent bone hyperplasia is a prevalent joint condition primarily affecting aging adults.The pathophysiology of KOA remains poorly understood,as it involves complex mechanisms that result in the same outcome.Consequently,researchers are interested in studying KOA and require appropriate animal models for basic research.Chinese herbal compounds,which consist of multiple herbs with diverse pharmacological properties,possess characteristics such as multicomponent,multipathway,and multitarget effects.The potential benefits in the treatment of KOA continue to attract attention.Purpose:This study aims to provide a comprehensive overview of the advantages,limitations,and specific considerations in selecting different species and methods for KOA animal models.This will help researchers make informed decisions when choosing an animal model.Methods:Online academic databases(e.g.,PubMed,Google Scholar,Web of Science,and CNKI)were searched using the search terms“knee osteoarthritis,”“animal models,”“traditional Chinese medicine,”and their combinations,primarily including KOA studies published from 2010 to 2023.Results:Based on literature retrieval,this review provides a comprehensive overview of the methods of establishing KOA animal models;introduces the current status of advantages and disadvantages of various animal models,including mice,rats,rabbits,dogs,and sheep/goats;and presents the current status of methods used to establish KOA animal models.Conclusion:This study provides a review of the animal models used in recent KOA research,discusses the common modeling methods,and emphasizes the role of traditional Chinese medicine compounds in the treatment of KOA.

Extracellular vesicles derived from mesenchymal stem cells mediate extracellular matrix remodeling in osteoarthritis through the transport of microRNA-29a

BACKGROUND Knee osteoarthritis(KOA)is a common orthopedic condition with an uncertain etiology,possibly involving genetics and biomechanics.Factors like changes in chondrocyte microenvironment,oxidative stress,inflammation,and immune responses affect KOA development.Early-stage treatment options primarily target symptom relief.Mesenchymal stem cells(MSCs)show promise for treatment,despite challenges.Recent research highlights microRNAs(miRNAs)within MSC-released extracellular vesicles that can potentially promote cartilage regeneration and hinder KOA progression.This suggests exosomes(Exos)as a promising avenue for future treatment.While these findings emphasize the need for effective KOA progression management,further safety and efficacy validation for Exos is essential.AIM To explore miR-29a’s role in KOA,we’ll create miR-29a-loaded vesicles,testing for early treatment in rat models.METHODS Extraction of bone marrow MSC-derived extracellular vesicles,preparation of engineered vesicles loaded with miR-29a using ultrasonication,and identification using quantitative reverse transcription polymerase chain reaction;after establi-shing a rat model of KOA,rats were randomly divided into three groups:Blank control group injected with saline,normal extracellular vesicle group injected with normal extracellular vesicle suspension,and engineered extrace-llular vesicle group injected with engineered extracellular vesicle suspension.The three groups evaluation,histological detection,and immunohistochemical detection to compare and evaluate the progress of various forms of arthritis.RESULTS General behavioral observation results showed that the extracellular vesicle group and engineered extracellular vesicle group had better performance in all four indicators of pain,gait,joint mobility,and swelling compared to the blank control group.Additionally,the engineered extracellular vesicle group had better pain relief at 4 wk and better knee joint mobility at 8 wk compared to the normal extracellular vesicle group.Imaging examination results showed that the blank control group had the fastest progression of arthritis,the normal extracellular vesicle group had a relatively slower progression,and the engineered extracellular vesicle group had the slowest progression.Gross histological observation results showed that the blank control group had the most obvious signs of arthritis,the normal extracellular vesicle group showed signs of arthritis,and the engineered extracellular vesicle group showed no significant signs of arthritis.Using the Pelletier gross score evaluation,the engineered extracellular vesicle group had the slowest progression of arthritis.Results from two types of staining showed that the articular cartilage of rats in the normal extracellular vesicle and engineered extracellular vesicle groups was significantly better than that of the blank control group,and the engineered extracellular vesicle group had the best cartilage cell and joint surface condition.Immunohistochemical detection of type II collagen and proteoglycan showed that the extracellular matrix of cartilage cells in the normal extracellular vesicle and engineered extracellular vesicle groups was better than that of the blank control group.Compared to the normal extracellular vesicle group,the engineered extracellular vesicle group had a better regulatory effect on the extracellular matrix of cartilage cells.CONCLUSION Engineered Exos loaded with miR-29a can exert anti-inflammatory effects and maintain extracellular matrix stability,thereby protecting articular cartilage,and slowing the progression of KOA.

Additional comments on extracellular vesicles derived from mesenchymal stem cells mediate extracellular matrix remodeling in osteoarthritis

Recently,we read an article published by the Yang et al.The results of this study indicated that engineered exosomes loaded with microRNA-29a(miR-29a)alleviate knee inflammation and maintain extracellular matrix stability in Sprague Dawley rats.The study’s results provide useful information for treating knee osteoarthritis(KOA).This letter,shares our perspectives on treating KOA using engineered exosomes for miR-29a.

Comparison between Care Strategies for Patients with Osteoarthritis of the Hands Based on the Use of Joint Protection, Assistive Technology and Exercises

Background: Osteoarthritis (OA) is a disabling disease that can affect 6% to 12% of the adult population and more than a third of people over 65 years of age. Purpose: To assess whether a group of people with hand osteoarthritis (hOA) who received different types of treatment improved their function after two years of follow-up. Method: The entire sample (n = 97) underwent three follow-up assessments regarding anthropometric parameters of the upper limbs and ability to perform functional activities. Subsequently, the sample was divided into two groups for the intervention periods, called the First Period (n = 73) and the Second Period (n = 24);the First Period kept the same protocol with orientations, and the Second Period went to an intervention with orientation strength exercises and use of orthosis. Findings: In the separate analysis of the three questions of the DASH pain module, no differences were found between the assessment moments for groups of guidelines, treatment, or symptoms. Significant effects were observed for F(2, 162) = 3.5, p = 0.033, η2 = 0.04, and interaction for moments and intervention F(2, 162) = 4.3, p = 0.016, η2 = 0.05. Implications: It can be concluded that only guidance treatment does not benefit patients with hand osteoarthritis. In contrast, guidance, exercise, and orthosis treatment can significantly improve the disease.

Carbamazepine in osteoarthritis treatment:A novel approach targeting Nav1.7 channels

Osteoarthritis(OA)presents a growing health concern,with substantial societal and healthcare burdens.Current management focuses on symptom relief,lacking disease-modifying options.Emerging research suggests the sodium channel Nav1.7 as a pivotal target in OA treatment.Preclinical studies demonstrate carbamazepine's efficacy in Nav1.7 blockade,offering significant joint protection in animal models.However,human trials are needed to validate these findings.Carbamazepine's repurposing holds promise for OA management,potentially revolutionizing treatment paradigms.Further research is essential to bridge the gap between preclinical evidence and clinical application,offering hope for improved OA management and enhanced patient quality of life.

Thoracic spine infection caused by Pseudomonas fluorescens:A case report and review of literature

BACKGROUND The clinical incidence of spinal infection is gradually increasing,and its onset is insidious,easily leading to missed diagnosis and misdiagnosis,which may lead to serious complications such as nervous system dysfunction,spinal instability and/or deformity,and cause a huge burden on society and families.Early identification of the causative agent and precision medicine will greatly reduce the suffering of patients.At present,the main pathogenic bacteria that cause spinal infection are Staphylococcus aureus,Streptococcus,Pneumococcus,Escherichia coli,and Klebsiella.There are no reports of spinal infection caused by Pseudomonas fluorescens.CASE SUMMARY We report a 32-year-old female patient with spinal infection.She presented with flank pain,initially thought to be bone metastases or bone tuberculosis,and had a family background of tumors.Her clinical features and changes in imaging and laboratory tests led to the suspicion of thoracic spine infection.Histopathology of the lesion showed inflammation,tissue culture of the lesion was negative several times,and the possible pathogen-Pseudomonas fluorescens was found after gene sequencing of the lesion.The patient recovered completely after a full course of antibiotic treatment.CONCLUSION This report increases the range of pathogens involved in spinal infections,highlights the unique advantages of gene sequencing technology in difficult-todiagnose diseases,and validates conservative treatment with a full course of antibiotics for spinal infections without complications.

Recent research progress from biological perspective on the mechanism of formation of osteoarthritis after anterior cruciate ligament injury

The anterior cruciate ligament(ACL)mainly plays a role in stabilizing the knee joint by limiting the forward translation of tibial force and rotational force at the tibial joint,and if this ligament is damaged,it will cause joint pain,limited mobility,knee instability,etc.According to related studies,the incidence of traumatic osteoarthritis(PTOA)after ACL injury is as high as 87%,although many studies have shown that patients with ACL injury are susceptible to PTOA,but the exact mechanism is currently unknown.This may be related to biological,structural,and mechanical factors caused by the ligament injury.Previous studies have shown that elevated inflammatory mediators in the joint cavity following ACL injury can lead to chondrocytes necrosis and degradation of the cartilage matrix.These potential biochemical mediators contribute to PTOA formation,and early intervention can reduce future episodes of PTOA.In recent years,many scholars have devoted themselves to studying the potential important factors and signaling pathways involved in the formation of osteoarthritis after ACL injury,and exploring its molecular mechanism,which has led to great progress in this field.This paper mainly studies and discusses the mechanism of osteoarthritis formation after ACL injury from the biological perspective.

Surgeon preferences in the treatment of thumb carpometacarpal osteoarthritis

BACKGROUND Primary thumb carpometacarpal(CMC)osteoarthritis is one of the most common conditions encountered by hand surgeons.Of the vast number of operations that have been proposed,none have demonstrated results significantly superior to trapeziectomy alone.AIM The purpose of our study was to determine why surgeons opt for their technique in treating CMC arthritis.METHODS A cross-sectional survey of active members of the American Society for Surgery of the Hand was conducted to evaluate the reasons behind their preferred technique in the treatment of isolated thumb CMC arthritis.Surgeons were contacted by email once and provided with a link to a de-identified survey consisting of 5 treatment questions and 5 demographic questions.RESULTS Of 950 responses were received.40.5%of surgeons preferred trapeziectomy+ligament reconstruction tendon interposition(LRTI),followed by trapeziectomy+suspensionplasty(28.2%),suture button suspension(5.9%),trapeziectomy alone(4.6%),prosthetic arthroplasty(3.2%),arthrodesis(1.1%),and other(6.6%).Proponents of trapeziectomy+LRTI cited familiarity(73.2%),exposure during fellowship(48.8%)and less proximal migration(60%)to be the main reasons affecting their decision.Surgeons who preferred trapeziectomy+suspensionplasty most reported simplicity(74.9%),fewer complications(45.3%),less proximal migration(43.8%),and avoidance of autogenous tissue harvest(42.7%).Advocates of suture button suspension cited avoidance of autogenous tissue harvest(80.4%),shorter immobilization(76.8%),and quicker recovery(73.2%)with their technique.Advocates of trapeziectomy alone cited simplicity(97.7%),fewer complications(86.4%),and avoidance of autogenous tissue harvest(59.1%).In their comments,45%of surgeons choosing trapeziectomy alone cited evidence as an additional rationale.Advocates of prosthetic arthroplasty cited improved pinch strength(83.3%)and improved range of motion(63.3%),while those preferring arthrodesis cited better pinch strength(90%)and frequently in their comments,durability.Of the surgeons who preferred a technique other than LRTI,41.8%reported they had tried LRTI in the past,citing complexity of the procedure,flexor carpi radialis harvest,and longer operative time as reasons for moving on.CONCLUSION Our study provides an update on current treatment trends and offers new insight into the reasons behind surgeons'decision making in the management of thumb carpometacarpal osteoarthritis.Despite strong Level 1 evidence supporting the use of trapeziectomy alone,our findings demonstrate that most surgeons continue to supplement trapeziectomy with other techniques such as LRTI or suspensionplasty.Several factors including familiarity,personal experience(Level 4 evidence),and comfort may be more influential than Level 1 evidence in determining the techniques in a surgeon's armamentarium.Further prospective studies are needed to determine the optimal technique for surgical management of Eaton stages II-IV CMC arthritis and how these studies will affect surgeons’choice.

Unicompartmental knee arthroplasty vs high tibial osteotomy for knee osteoarthritis:A comparison of clinical and radiological outcomes

BACKGROUND Unicompartmental knee arthroplasty(UKA)and high tibial osteotomy(HTO)are well-established operative interventions in the treatment of knee osteoarthritis.However,which intervention is more beneficial to patients with knee osteoarthritis remains unknown and a topic of much debate.Simultaneously,there is a paucity of research assessing the relationship between radiographic parameters of knee joint alignment and patient-reported clinical outcomes,preoperatively and following HTO or UKA.AIM To compare UKAs and HTOs as interventions for medial-compartment knee osteoarthritis:Examining differences in clinical outcome and investigating the relationship of joint alignment with respect to this.METHODS This longitudinal observational study assessed a total of 42 patients that had undergone UKA(n=23)and HTO(n=19)to treat medial compartment knee osteoarthritis.Patient-reported outcome measures(PROMs)were collected to evaluate clinical outcome.These included two disease-specific(Knee Injury and Osteoarthritis Outcome Score,Oxford Knee Score)and two generic(EQ-5D-5L,Short Form-12)PROMs.The radiographic parameters of knee alignment assessed were the:Hip-knee-ankle angle,mechanical axis deviation and angle of Mikulicz line.RESULTS Statistical analyses demonstrated significant(P<0.001),preoperative to postoperative,improvements in the PROM scores of both groups.There were,however,no significant inter-group differences in the postoperative PROM scores of the UKA and HTO group.Several significant correlations associated a more distolaterally angled Mikulicz line with worse knee function and overall health preoperatively(P<0.05).Postoperatively,two clusters of significant correlations were observed between the disease-specific PROM scores and knee joint alignment parameters(hip-knee-ankle angle,mechanical axis deviation)within the HTO group;yet no such associations were observed within the UKA group.CONCLUSION UKAs and HTOs are both efficacious operations that provide a comparable degree of clinical benefit to patients with medial compartment knee osteoarthritis.Clinical outcome has a limited association with radiographic parameters of knee joint alignment postoperatively;however,a more distolaterally angled Mikulicz line appears associated with worse knee function/health-related quality of life preoperatively.

Intra-articular interventions in osteoarthritis:Navigating the landscape of hyaluronic acid,mesenchymal stem cells,and plateletrich plasma

Osteoarthritis(OA)poses a substantial burden on patients,leading to pain,functional decline,and reduced quality of life.While conventional treatments focus on symptom management,disease-modifying interventions are yet to be established.This review explores the efficacy of intra-articular interventions,particularly hyaluronic acid(HA),mesenchymal stem cells(MSCs),and platelet-rich plasma(PRP),in the context of OA management.HA injections,with diverse formulations like Hylan G-F20,sodium hyaluronate,and hyaluronan,present varying outcomes,necessitating a nuanced understanding of their effectiveness and timing.MSC therapy,derived from adipose tissue,umbilical cord,or bone marrow,shows promising results in clinical improvement,with adipose-derived MSCs demonstrating efficacy in maintaining benefits over 6 mo.Conversely,bone-marrow-derived MSCs show limited effectiveness,highlighting the need for sourcespecific considerations.PRP has emerged as a superior option for long-term pain reduction and quality of life improvement,with leukocyte-poor formulations and a critical platelet count of 10 billion demonstrating optimal results.This comprehensive analysis underscores the potential of intra-articular interventions in OA management,emphasizing the need for personalized and evidence-based approaches to enhance treatment efficacy and patient outcomes.

Scutellarein Ameliorated Chondrocyte Inflammation and Osteoarthritis in Rats

Objective:Osteoarthritis(OA)is a degenerative joint disorder characterized by the gradual degradation of joint cartilage and local inflammation.This study aimed to investigate the anti-OA effect of scutellarein(SCU),a single-unit flavonoid compound obtained from Scutellaria barbata D.Don,in rats.Methods:The extracted rat chondrocytes were treated with SCU and IL-1β.The chondrocytes were divided into control group,IL-1βgroup,IL-1β+SCU 50µmol/L group,and IL-1β+SCU 100µmol/L group.Morphology of rat chondrocytes was observed by toluidine blue and safranin O staining.CCK-8 method was used to detect the cytotoxicity of SCU.ELISA,qRT-PCR,Western blotting,immunofluorescence,SAβ-gal staining,flow cytometry,and bioinformatics analysis were applied to evaluate the effect of SCU on rat chondrocytes under IL-1βintervention.Additionally,anterior cruciate ligament transection(ACL-T)was used to establish a rat OA model.Histological changes were detected by safranin O/fast green,hematoxylin-eosin(HE)staining,and immunohistochemistry.Results:SCU protected cartilage and exhibited anti-inflammatory effects via multiple mechanisms.Specifically,it could enhance the synthesis of extracellular matrix in cartilage cells and inhibit its degradation.In addition,SCU partially inhibited the nuclear factor kappa-B/mitogen-activated protein kinase(NF-κB/MAPK)pathway,thereby reducing inflammatory cytokine production in the joint cartilage.Furthermore,SCU significantly reduced IL-1β-induced apoptosis and senescence in rat chondrocytes,further highlighting its potential role in OA treatment.In vivo experiments revealed that SCU(at a dose of 50 mg/kg)administered for 2 months could significantly delay the progression of cartilage damage,which was reflected in a lower Osteoarthritis Research Society International(OARSI)score,and reduced expression of matrix metalloproteinase 13(MMP13)in cartilage.Conclusion:SCU is effective in the therapeutic management of OA and could serve as a potential candidate for future clinical drug therapy for OA.

Adipose-derived regenerative therapies for the treatment of knee osteoarthritis

Knee osteoarthritis is a degenerative condition with a significant disease burden and no disease-modifying therapy.Definitive treatment ultimately requires joint replacement.Therapies capable of regenerating cartilage could significantly reduce financial and clinical costs.The regenerative potential of mesenchymal stromal cells(MSCs)has been extensively studied in the context of knee osteoarthritis.This has yielded promising results in human studies,and is likely a product of immunomodulatory and chondroprotective biomolecules produced by MSCs in response to inflammation.Adipose-derived MSCs(ASCs)are becoming increasingly popular owing to their relative ease of isolation and high proliferative capacity.Stromal vascular fraction(SVF)and micro-fragmented adipose tissue(MFAT)are produced by the enzymatic and mechanical disruption of adipose tissue,respectively.This avoids expansion of isolated ASCs ex vivo and their composition of heterogeneous cell populations,including immune cells,may potentiate the reparative function of ASCs.In this editorial,we comment on a multicenter randomized trial regarding the efficacy of MFAT in treating knee osteoarthritis.We discuss the study’s findings in the context of emerging evidence regarding adipose-derived regenerative therapies.An underlying mechanism of action of ASCs is proposed while drawing important distinctions between the properties of isolated ASCs,SVF,and MFAT.

Efficacy of stromal vascular fraction for knee osteoarthritis:A prospective,single-centre,non-randomized study with 2 years follow-up

BACKGROUND Current osteoarthritis(OA)treatments focus on symptom relief without addressing the underlying disease process.In regenerative medicine,current treatments have limitations.In regenerative medicine,more research is needed for intra-articular stromal vascular fraction(SVF)injections in OA,including dosage optimization,long-term efficacy,safety,comparisons with other treatments,and mechanism exploration.AIM To compare the efficacy of intra-articular SVF with corticosteroid(ICS)injections in patients with primary knee OA.METHODS The study included 50 patients with Kellgren-Lawrence grades II and III OA.Patients were randomly assigned(1:1)to receive either a single intra-articular SVF injection(group A)or a single intra-articular ICS(triamcinolone)(group B)injection.Patients were followed up at 1,3,6,12,and 24 months.Visual analog score(VAS)and International Knee Documentation Committee(IKDC)scores were administered before the procedure and at all followups.The safety of SVF in terms of adverse and severe adverse events was recorded.Statistical analysis was performed with SPSS Version 26.0,IBM Corp,Chicago,IL,United States.RESULTS Both groups had similar demographics and baseline clinical characteristics.Follow-up showed minor patient loss,resulting in 23 and 24 in groups A and B respectively.Group A experienced a notable reduction in pain,with VAS scores decreasing from 7.7 to 2.4 over 24 months,compared to a minor reduction from 7.8 to 6.2 in Group B.This difference in pain reduction in group A was statistically significant from the third month onwards.Additionally,Group A showed significant improvements in knee functionality,with IKDC scores rising from 33.4 to 83.10,whereas Group B saw a modest increase from 36.7 to 45.16.The improvement in Group A was statistically significant from 6 months and maintained through 24 months.CONCLUSION Our study demonstrated that intra-articular administration of SVF can lead to reduced pain and improved knee function in patients with primary knee OA.More adequately powered,multi-center,double-blinded,randomised clinical trials with longer follow-ups are needed to further establish safety and justify its clinical use.