Decreased chondrocyte features of articular cartilage during short-term repeated overloading: a synovium-cartilage interaction via inhibin subunit beta A

The primary goal of this study is to investigate the ultrashort-term responses and molecular mechanisms in both the synovium and cartilage under conditions of excessive mechanical loading, a major contributing factor in the pathogenesis of osteoarthritis (OA). While cartilage degeneration is a hallmark of OA, the involvement of the synovium in disease progression and pain, particularly in relation to synovitis, has been increasingly recognized. Despite this, the immediate molecular changes in both tissues following mechanical stress, and the interactions between them, remain unclear. To address these gaps, we developed a mouse model that simulates excessive mechanical loading through treadmill exercise combined with weight attachment. We investigated the ultrashort-term gene expression changes in the synovium and cartilage at 1, 4, and 24 hours post-exercise using RNA sequencing (RNA-seq). Additionally, we examined the effects of repeated overloading by analyzing tissue samples from mice subjected to four consecutive days of overloading. This approach allowed us to capture both the acute and repeated stress responses in these tissues. Through transcriptomic analysis, we aimed to identify key molecular mediators driving both the rapid transcriptional changes in each tissue and the synovium-cartilage interaction.