Regulation of Integrin signaling in chondrogenesis and osteoarthritis development.

Abstract

Basic research and clinical trials have investigated the function of integrin signaling in chondrocyte differentiation and cartilage disorders, although the exact functions of integrin signaling during chondrogenesis are not well understood. Integrin signaling is necessary for cartilage development, as the loss of known mediators of integrin signaling causes abnormal cartilage and endochondral bone formation. In contrast, integrin-extracellular matrix (ECM) contacts promote the dedifferentiation of cultured primary chondrocytes, and several studies suggest that integrin signaling serves different roles depending on the chondrogenic stage. Furthermore, integrin signaling is a key source of the inflammatory reactions responsible for joint destruction. Given the ECM-rich environment and the expression of multiple integrin subunits, it is challenging for chondrocytes to minimize integrin-ECM interactions to allow chondrogenic differentiation to proceed and also maintain chondrogenic properties and protect from dedifferentiation or destructive signals. Here, we found a secreted integrin modulator expressed in prechondrocytes and promoting chondrogenesis in vertebrate. Integrin signaling is not only involved in cartilage disorders, but also contributes to various other human disorders such as inflammatory bowel disease, cardiovascular disorders, and cancers. Our discovery on a unique secreted integrin modulator should attract attention from researchers in many fields of biomedical science and will lead to new approaches for treating integrin-related human diseases, including destructive cartilage disorders.