Osteomodulin down-regulation is associated with osteoarthritis development

Abnormal subchondral bone remodeling leading to sclerosis is a main feature of osteoarthritis (OA) and Osteomodulin (OMD), a proteoglycan involved in extracellular matrix mineralization, is associated to the sclerotic phenotype. However, the functions of OMD remain poorly understood, specifically in vivo. We used knock-out and overexpressing male mice for Omd and mutant zebrafish to study its roles in bone and cartilage metabolism and in the development of OA. The expression of Omd is deeply correlated to bone and cartilage microarchitectures affecting the bone volume and the onset of subchondral bone sclerosis and spontaneous cartilage lesions. Mechanistically, OMD binds to RANKL and inhibits osteoclastogenesis; thus controlling the balance of the bone remodeling. In conclusions, OMD is a key factor in subchondral bone sclerosis associated with OA. It participates in bone and cartilage homeostasis acting on the regulation of osteoclastogenesis. Targeting OMD may be a promising new and personalized approach for OA.