Osteoarthritis and Cartilage最新文献

Objective: Previous cyclical compressive fatigue studies in cartilage either incorporated concurrent sliding or, when sliding was absent, did not directly compare synovial fluid (SF) and phosphate-buffered saline (PBS) as bathing solutions. Here, we isolate the effect of SF by eliminating the putative influence of sliding. We hypothesize that SF delays the onset of delamination wear by reducing fatigue failure under pure cyclical compressive loading.

Design: This study compared the fatigue failure rate of cartilage plugs under four bath conditions: PBS versus SF (Experiment 1), and 25% SF/PBS versus 50% SF/PBS (Experiment 2). Immature bovine cartilage contralateral femoral condyle samples were tested in a custom-built solenoid-driven cyclical compression device that continuously recorded load. A compressive load of 54.2 ± 0.7 N was applied at 2 Hz with a plano-convex glass lens (∅12.5 mm) for up to 36,000 cycles. Experiments 1 and 2 each included 8 cylindrical plugs per group (∅12 mm). Tests were terminated at 12,000 cycles if gross damage was observed; otherwise, tests proceeded to 36,000 cycles (5 h). Damage was evaluated by photography, contact area measurement, and surface roughness at baseline, 12,000, and 36,000 cycles.

Results: In Experiment 1, all PBS samples failed by 12,000 cycles, whereas all SF samples remained intact through 36,000 cycles. In Experiment 2, 5 of 8 plugs failed in the 25% SF/PBS group, and 2 of 8 plugs failed in the 50% SF/PBS group. The average surface roughness (R_q) increased significantly in PBS: from 0.025 ± 0.003 mm at baseline to 0.068 ± 0.023 mm at test completion (p < 0.0001). In 25% SF/PBS, R_q rose from 0.024 ± 0.002 mm to 0.039 ± 0.013 mm (p < 0.01). In contrast, no significant change was observed in SF (0.024 ± 0.003 mm to 0.023 ± 0.001 mm; p > 0.99) or in 50% SF/PBS (0.023 ± 0.004 mm to 0.027 ± 0.005 mm; p = 0.45). PLM and histology confirmed cartilage failure by delamination, in all PBS samples and in damaged diluted-SF samples, while no damage was detected in SF. Delamination always occurred in the middle zone of the articular layer.

Conclusions: SF protects cartilage from fatigue failure under cyclical compressive loading, independent of any putative role in reducing friction between articular surfaces. Higher SF concentrations were associated with progressively lower fatigue failure rates, underscoring a critical protective function against fatigue failure, rather than boundary lubrication alone.

Objective: To evaluate the responsiveness of objective, quantifiable physiological or behavioural data measures (digital biomarkers) as outcome measures for people living with hip and/or knee osteoarthritis (OA) in community or home settings.

Methods: This systematic review and meta-analysis identified eligible studies from four electronic databases. Studies were required to use a digital biomarker as an outcome measure or had data collected by a portable or wearable device, usable at home, and without expert oversight (e.g., accelerometers, smartphone devices), and collected at a minimum of two time points. Two independent reviewers conducted screening and data extraction. A meta-analysis was performed using a random-effects model. Results were reported as standardized response means (SRMs) and 95% confidence intervals (CIs). Subgroup analyses were conducted based on intervention versus non-intervention groups and across different time periods (short, medium, long-term). Risk of bias was assessed using modified criteria for evidence quality.

Results: We identified 40 studies evaluating 18 digital biomarkers. Participants had a mean age of 64 (SD=4) years, with most having knee OA. The overall quality of the studies was high. Accelerometers (95%) were the most commonly used technology type. Mobility related outcomes were the most responsive digital biomarker domain. Cadence, walking speed, and step count showed moderate (SRM = 0.65, 95% CI: 0.42-0.87), small (SRM = 0.43, 95% CI: 0.15-0.70), and trivial (SRM = 0.19, 95% CI: 0.02-0.36) degrees of responsiveness, respectively. Energy expenditure demonstrated a trivial negative responsiveness (SRM = -0.16, 95% CI: -0.31 to -0.01). All digital biomarkers identified were based on land-based activities, which limits their application for monitoring non-land-based activities such as water exercises, cycling, Tai Chi, yoga or sleep.

Conclusions: Digital biomarkers related to mobility measures, have the potential for greater uptake in OA clinical trials to assess mobility health in community and home-settings.

Systematic review registration: PROSPERO ID: CRD42024600515.

Objective: Multiple epiphyseal dysplasia (MED), caused by mutations in MATN3, is a chondrodysplasia affecting the cartilage growth plate and is characterised by delayed epiphyseal ossification, short stature, and early onset osteoarthritis. Here we generated an in vitro human pluripotent stem cell (hPSC) model of cartilage growth-plate development to identify pathogenic mechanisms underlying MED.

Design: hPSCs were differentiated to chondrocytes via a mesenchymal intermediate, followed by TGFβ3+BMP2 induced chondrogenic pellet culture. MATN3-mutant hPSCs were generated by reprogramming MED patient PBMCs or by CRISPR-Cas9 gene editing to introduce a MATN3 mutation in a hESC line. RNAseq was used to assess chondrogenesis and identify MED pathogenic mechanisms. Transmission electron microscopy (TEM) was used to assess extracellular matrix assembly.

Results: The resultant hPSC-derived cartilage pellets displayed a typical cartilage morphology and strongly expressed cartilage matrix markers, e.g., collagen II and matrilin-3. Matrilin-3 protein was detected within both the matrix and cells of heterozygous mutant hPSC-cartilage pellets. RNAseq of mutant hPSC-cartilage pellets revealed significant enrichment for 'ECM organisation' and 'cholesterol biosynthesis' pathway genes as well as sightly increased expression of some unfolded protein response (UPR) marker genes. MATN3 mutant hPSC-derived cartilage pellets displayed abnormal matrix assembly, distended ER, accumulation of lipid droplets, and increased cholesterol content.

Conclusion: Our model revealed mutant matrilin-3 induces cholesterol biosynthesis pathway upregulation and abnormal matrix assembly during MED pathogenesis. This study provides new insights into the molecular mechanisms underlying MED and highlights potential therapeutic targets.