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.