CARTILAGE最新文献

ObjectiveTo determine whether telopeptides of collagen type II could induce osteoarthritic tissue damage via receptor for the native protein by using human articular cartilage.MethodsCartilage slices were harvested from patients receiving total arthroplasty. Cartilage tissue cultures or primary chondrocyte cultures were treated with 30 µM N- or C-telopeptide (NT or CT) for 7 days or for 24 h. Loss of proteoglycan (PG) from cartilage was evaluated with 1,9-dimethylmethylene blue (DMMB) assay. Conditioned media or cell lysates were measured for levels of matrix metalloproteinases (MMPs), MMP-3 and MMP-13, or integrin beta-1 (ITGB1) with Western blotting or real-time polymerase chain reaction (PCR).ResultsEither NT or CT could induce significant loss of PG from cartilage than did phosphate-buffered saline (PBS), the delivery vehicle (18.45 ± 6.58 or 15.50 ± 4.91 µg PG/mg wet cartilage treated by NT or CT vs. 25.61 ± 4.14 µg PG/mg wet cartilage treated by PBS; P = 0.037 for NT, P = 0.004 for CT). Upregulation of MMP-3 and MMP-13 was induced by either NT or CT at 24 h (chondrocyte cultures) or Days 4 and 7 post-treatment (cartilage cultures). CT-induced stronger expression of ITGB1 in chondrocytes than did NT.ConclusionTelopeptides of collagen type II could damage human articular cartilage and upregulate MMP-3 and MMP-13. The catabolic effect of CT might be mediated by ITGB1.

AimsPrecise evaluation of cartilage damage is essential for the better management of osteoarthritis and treatment of articular cartilage. For accurate evaluation of cartilage damage, direct visual and/or histological assessment of articular cartilage is preferred over radiological or magnetic resonance imaging (MRI) imaging. This study aimed to determine whether, and to what extent, visual macroscopic grading using International Cartilage Repair Society (ICRS) system correlates with microscopic evaluation using the Osteoarthritis Research Society International (OARSI) histopathological scoring in an ex-vivo setting.MethodsA total of 70 articular cartilage sections obtained from 19 osteoarthritic human knees were macroscopically classified using the ICRS grading system and subsequently evaluated histologically using the OARSI scoring system. Spearman's correlation and bivariate linear regression analyses were performed to assess the association between ICRS and OARSI scores. The reproducibility, reliability, and inter- and intra-observer consistency of the OARSI scoring were further evaluated using Bland-Altman analysis, correlation coefficients, Cohen's kappa, Cronbach's alpha, and intraclass correlation coefficients (ICC).ResultsQualitative assessment revealed a progressive increase in OARSI histological scores corresponding to higher ICRS grades. Spearman's correlation and regression analyses demonstrated a weak positive correlation between visual ICRS grading and histological OARSI scoring in early-stage lesions (ICRS grades 0-I; n = 29, r = 0.592, R² = 0.350, p < 0.001), a moderate correlation with the inclusion of moderate-stage lesions (ICRS grades 0-II; n = 47, r = 0.603, R² = 0.364, p < 0.001), and a strong correlation when severely degenerated cartilage was included (ICRS grades 0-III; n = 67, r = 0.811, R² = 0.657, P < 0.001). The analysis of histological OARSI scores demonstrated narrow limits of agreement and minimal inter-observer variability in the Bland-Altman plot, excellent inter- and intra-observer agreement (ICC > 0.85), and almost perfect reliability (Cronbach's α > 0.95).ConclusionThe results of the study demonstrated a stage-dependent association between macroscopic and histological assessments of osteoarthritic cartilage. The findings indicate that macroscopic ICRS grading may serve as a reliable tool for evaluating moderate to advanced stages of cartilage degeneration. However, its utility in early-stage lesions appears limited due to a weaker correlation with OARSI histological scores. Thus, while macroscopic visual evaluation should be interpreted with caution in early-stage degeneration, histological assessment using the OARSI scoring system remains a valuable tool for accurately identifying early degenerative changes.

BackgroundViscosupplementation (VS) by intra-articular injections of hyaluronic acid (HA) is an increasingly used treatment of hip osteoarthritis (OA). However, there are no clear European recommendations for its use.MethodsTwelve members of the European Viscosupplementation Consensus Group (EUROVISCO), made up of rheumatologists, orthopedic surgeons, and rehabilitation physicians from European countries, were asked to make a therapeutic decision on 23 statements based on an exhaustive analysis of the literature and their clinical experience, using the Delphi method. For each statement, the strength of agreement and the level of consensus were calculated by the chairman of the groupResultsThe expert panel reached unanimous or high consensus, either for or against, on 16 of the proposed statements. The main ones are: Current evidence and the results of observational trials support the use of VS in patients with hip OA who do not require surgery. VS is more effective in cases of mild to moderate hip OA. Hip VS is safe and well tolerated, even with repeated injections. The outcome of VS depends on the viscosupplement used. A standard X-ray must be obtained before deciding on VS. VS must be performed under imaging guidance. A single injection regimen is preferable to repeat injections. VS can be considered for individuals who wish to postpone surgery. Hip replacement surgery should not be performed within 3 months of VS. VS should not be used to treat an osteoarthritis flare. VS is part of a multimodal treatment for hip OA.ConclusionThis set of recommendations is intended to help practitioners make decisions about HA VS in patients with OA.

ObjectiveDamage to the joint-surface repair itself as fibrocartilage, a mixture of cartilaginous and fibrous tissues, which leads to debilitating conditions with persistent joint pain. The regulatory mechanisms that control the formation of these tissues are poorly understood.MethodsWe analyzed single-cell RNA-sequencing data from the repaired tissue formed in a chondral defect model of the monkey knee joint to identify genes specifically expressed in the repaired tissue. We used primary chondrocytes from semaphorin 7A (Sema7A) knockout mice to analyze the function of Sema7A in the dedifferentiation of chondrocytes in vitro. We introduced articular cartilage defect model in the knee joints in Sema7A knockout mice.ResultsSingle-cell RNA-sequencing analysis revealed that Sema7A is specifically expressed in the cartilaginous tissue in the repaired tissue formed in the articular cartilage defect. In vitro analysis showed that Sema7A autonomously induced the dedifferentiation of chondrocytes at passage 2, which is assumed to correspond to cartilaginous tissue cells, toward a fibroblastic state. In addition, Sema7A heteronomously suppressed the re-differentiation of passage 8 fibroblastic cells, which were assumed to correspond to fibrous tissue cells. Addition of anti-integrin β1 neutralizing antibody abolished Sema7A-induced suppression of Col2a1 and Col9a1 expression, suggesting that integrin β1 mediates Sema7A function. Sema7A knockout mice showed significantly improved healing in an articular surface defect model of the knee joints. Sema7A deletion increased cartilaginous tissue formation and decreased fibrous tissue formation in joint-surface defects.ConclusionsSema7A regulates the balance between cartilaginous and fibrous tissues during articular cartilage damage repair.

ObjectiveTo systematically synthesize clinical, structural, biomarker, and safety outcomes of knee joint distraction (KJD) and implantable medial compartment shock absorbers (ISA) for tibiofemoral knee osteoarthritis (KOA), and to summarize comparative evidence versus arthroplasty, high tibial osteotomy (HTO), orthoses, and non-operative care.DesignA PRISMA-based systematic review of PubMed, EMBASE, Scopus, and Cochrane Library from inception to 1 October 2025 identified peer-reviewed clinical studies of KJD or ISA for tibiofemoral KOA. Two reviewers independently screened records, extracted data, and assessed risk of bias. Owing to substantial clinical and methodological heterogeneity and overlapping cohorts, a narrative synthesis was prespecified and no quantitative meta-analysis was performed.ResultsSeventeen studies (13 KJD, 4 ISA) reporting on approximately 400 patients met the inclusion criteria. KJD yielded clinically important 1- to 2-year improvements in WOMAC/KOOS and VAS pain, with arthroplasty-free survival of roughly 75% to 85% at 5 to 9 years in selected series, accompanied by increases in radiographic joint-space width and MRI-derived cartilage thickness in the most affected compartment. ISA consistently improved WOMAC pain and function and showed higher 2-year arthroplasty-free survival than HTO or non-operative comparators.ConclusionsCurrent evidence, based on small heterogeneous cohorts at low-to-moderate certainty, suggests that KJD and ISA can provide meaningful short- to mid-term symptom relief and delay arthroplasty in carefully selected patients. KJD and ISA address different indications and mechanisms and should be considered complementary rather than interchangeable joint-preserving strategies. Larger, independently replicated randomized trials with standardized structural and clinical endpoints are needed before widespread adoption.

Purpose: People who sustain joint injuries such as anterior cruciate ligament (ACL) rupture often go on to develop post-traumatic osteoarthritis (PTOA). ACL injuries are often treated with ACL reconstruction, but there is typically a gap of several weeks between injury and surgery. However, it is unclear how loading or unloading of the injured joint during the early postinjury period affects the progression of PTOA. The goal of this study was to determine how unloading between noninvasive ACL injury and surgical restabilization of the injured joint affects PTOA progression in mice.

Findings: Mice were subjected to noninvasive ACL injury or no injury followed by 1 week of hindlimb unloading (HLU) or normal cage activity. After 1 week of HLU or cage activity, mice underwent restabilization surgery or no surgery. ACL injury resulted in considerable epiphyseal trabecular bone loss regardless of HLU or cage activity. HLU groups exhibited significantly reduced chondrophyte/osteophyte formation, OA scoring, and synovitis at day 42. Single-cell RNA sequencing revealed that 1 week of HLU resulted in more neutrophils and less monocytes-macrophages in the injured joint.

Conclusions: This study establishes that 1 week of HLU after ACL injury effectively slowed PTOA progression, suggesting that the early inflammatory response and joint instability play a key role in PTOA initiation and progression, and neutrophils and monocytes-macrophages play roles in the modulation. However, subsequent joint restabilization surgery caused greater inflammatory protease activity in the joint and exacerbated the loss of epiphyseal trabecular bone but did not significantly diminish OA score or synovitis.

BackgroundMatrix-induced autologous chondrocyte implantation (MACI) relies on secure collagen membrane fixation for successful cartilage repair. However, comparative biomechanical data on fixation techniques remain limited.ObjectiveTo evaluate and compare the fixation strength of various collagen membrane fixation techniques used in autologous chondrocyte implantation (ACI) using an in vitro porcine model.DesignFifty porcine knees were used to test 17 different fixation methods for securing collagen membranes (Chondro-Gide®). Fixation techniques included various combinations of absorbable and non-absorbable anchors, different suture materials, knotted and knotless techniques, and absorbable pins. Membrane thickness was measured using digital micrometry. Tensile testing was performed using a digital force gauge until failure. Peak fixation strength and failure modes were recorded. Results. Mean collagen membrane thickness was 0.492 ± 0.151 mm with moderate correlation to tensile strength (r = 0.554, P < 0.001). Among tested methods, the 2.0-mm absorbable pin demonstrated significantly superior fixation strength compared to all other techniques (16.67 ± 4.17 N vs. 5.54-10.01 N, P < 0.01). No significant differences were observed among various anchor-suture combinations. Failure occurred predominantly through membrane tearing at anchor insertion sites (47.1%) and suture fixation points (35.9%), rather than anchor pull-out or suture breakage.ConclusionsMost conventional fixation methods showed comparable mechanical performance, limited by the inherent properties of the collagen membrane. The 2.0-mm absorbable pin achieved superior fixation through a compression-embedding mechanism rather than simple surface fixation. These findings suggest that fixation strategies incorporating membrane compression into the subchondral bone may provide enhanced mechanical stability for ACI procedures.

ObjectiveHypertonic injection of dextrose is an alternative treatment for reducing pain and increasing function in patients with knee osteoarthritis (OA). Dextrose prolotherapy (DP) is hypothesized to induce localized inflammation, leading to proliferation of cells in the joint space. This in vitro study explores how exposure to therapeutic doses of hypertonic dextrose affects fibroblast viability and proliferation, either directly or indirectly through exposure to secreted factors by dextrose-treated cells.DesignMRC-5 fibroblasts exposed for 15 to 120 minutes to dextrose solutions at concentrations of 5%, 10%, 15%, 20%, or 25% were compared to a media-only control. Metabolic activity was measured by the XTT assay as an indicator of cell viability and proliferation.ResultsFibroblasts exposed for any length of time at the highest concentration of dextrose (25%) or lower concentrations (10-20%) for longer durations exhibited significant reductions in cell viability compared to media controls. However, fibroblasts exposed to higher concentrations of dextrose (15-25%) for shorter durations (30-60 min) or lower concentrations (10%) for longer durations (120 min) exhibit an increased proliferative effect 48 hours after the initial experiment. Nascent fibroblasts exposed to supernatant fluid from cells directly treated with dextrose did not have a negative impact on cell viability compared to the media control.ConclusionsThese results suggest dextrose concentrations used for prolotherapy may stimulate proliferative responses in fibroblasts in support of theorized mechanisms of DP.

ObjectiveTo compare the dose-dependent chondrotoxicity of tranexamic acid (TXA) and aminocaproic acid (ACA) in vitro and in vivo.DesignIn vitro, human chondrocytes were exposed to TXA or ACA (0-50 mg/ml), and cytotoxicity was assessed. In vivo, a rat model of monoiodoacetate-induced osteoarthritis was used to evaluate cartilage damage following intra-articular injections of TXA or ACA.ResultsIn vitro, both TXA and ACA reduced chondrocyte viability in a dose-dependent manner, with significant cytotoxicity observed at concentrations ≥20 mg/ml. TXA was more toxic than ACA at these higher concentrations. Apoptosis increased markedly at 30 mg/ml for both agents. In the rat osteoarthritis model, joints treated with TXA or ACA showed greater cartilage erosion and matrix loss compared to controls, with TXA causing more severe damage.ConclusionBoth TXA and ACA are chondrotoxic in a dose-dependent manner, with TXA demonstrating greater potency. Lower concentrations (≤10 mg/ml) are recommended for topical use in cartilage-preserving surgery to minimize potential damage.

IntroductionKnee chondral defects are a common cause of pain and dysfunction. This study assessed the prevalence of spin and methodological quality of systematic reviews and meta-analyses on knee chondral defects in orthopedic literature.MethodsFollowing PRISMA guidelines, a systematic review was conducted in May 2025 using PubMed, Web of Science, and Embase. Reviews addressing knee chondral defects in orthopedics were included. Abstracts were evaluated for 15 spin types, and methodological quality was rated using AMSTAR 2. Data on PRISMA adherence, publication year, and Level of Evidence were extracted. Associations between study characteristics and spin were analyzed using t tests, ANOVA, Fisher's exact tests, and Spearman's rank correlations.ResultsOf 238 studies identified, 21 reviews met criteria. Spin was present in 18 (85.7%). The most common types were type 3 (66.7%), type 5 (57.1%), and type 1 (52.4%). Misleading reporting occurred in 85.7%, misleading interpretation in 81.0%, and extrapolation in 52.4%. AMSTAR 2 rated 95.2% as "critically low" and 4.8% as "moderate." Journal impact factor correlated with spin presence (P = 0.016) and greater number of spin types (P = 0.012).Discussion/ConclusionMost reviews on knee chondral defects contained spin and were of poor quality, underscoring the need for critical appraisal and improved reporting.