Short-term overloading exercise attenuates articular chondrocyte features partly via synovium-cartilage interactions...

Excessive mechanical loading leads to cartilage degeneration. However, short-term responses of the synovium and cartilage to overloading and interactions between these tissues remain poorly understood. We developed a mouse model to study excessive mechanical loading, combining treadmill exercise with weight attachment. Time-course RNA sequencing of the synovium and cartilage displayed transient upregulation of inflammation after single overloading, whereas it was prolonged by repeated overloading. Ingenuity pathway analysis identified Inhba, encoding inhibin subunit beta A, as an upstream molecule for the cartilage transcriptomic changes. Inhba was highly induced by single or repeated overloading in the synovium, and Inhba protein was detected in the superficial layer of the synovium. Supplementation with recombinant activin A, a homodimer of Inhba, exerted catabolic effects in mouse primary chondrocytes. Further insights into mechano-responses of the synovium and cartilage, including the role played by Inhba in the synovium-cartilage interaction, may contribute to the elucidation of osteoarthritis pathogenesis.