Study on the Detection of Synovial Matrix Stiffness in Mice with Osteoarthritis and Its Impact on the Expression of RAB27A in Synovial Fibroblasts.

PURPOSE:To investigate the changes in synovial matrix stiffness in a mouse model of osteoarthritis (OA) and the expression of RAB27A, a key regulator of exosome biosynthesis, in synovial fibroblasts, and to validate the effect of matrix stiffness on RAB27A expression in vitro. METHODS:OA was induced in mouse knees by anterior cruciate ligament transection combined with medial meniscus destabilization (ACLT+DMM). Modeling efficacy was confirmed by Micro-CT, histology, and immunofluorescence. Synovial matrix stiffness was assessed by using nanoindentation. Mouse synovial fibroblasts were cultured on PEGDMA hydrogels with different stiffness, and RAB27A expression was detected by westernblot. RESULTS:Compared with the control group, the OA group exhibited a significant increase in synovial Young's modulus (~64%, p < 0.05), along with a ~ 1.53 fold increase in RAB27A-positive cells (p < 0.001). RAB27A expression showed a strong positive correlation with matrix stiffness (r = 0.671, p < 0.01). In vitro, the expression of RAB27A, MMP13, and COX2 was significantly upregulated in synovial fibroblasts cultured on stiff PEGDMA hydrogels, confirming a direct regulatory effect of matrix stiffness on exosome-related protein expression. CONCLUSIONS:Increased synovial matrix stiffness in OA may upregulate RAB27A expression, potentially regulating exosome secretion in synovial fibroblasts. This reveals a novel mechano-biological coupling mechanism in OA synovitis.