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 with the scleroti...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 with the sclerotic phenotype. However, the functions of OMD remain poorly understood, specifically in vivo. We used Omd knockout and overexpressing male mice 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 with 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 bone remodeling. In conclusion, OMD is a key factor in subchondral bone sclerosis associated with OA. It participates in bone and cartilage homeostasis by acting on the regulation of osteoclastogenesis. Targeting OMD may be a promising new and personalized approach for OA.展开更多
基金funded by the F.R.S.-FNRS for the “EOS: The Excellence of Science-Join-t-against-Osteoarthritis”, grant number 30480119by a research grant from the Osteoarthritis Foundation and by the University of Liege (Fonds Léon Fredericq and Fonds Speciaux à la Recherche)funded by Versus Arthritis senior fellowship 21937。
文摘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 with the sclerotic phenotype. However, the functions of OMD remain poorly understood, specifically in vivo. We used Omd knockout and overexpressing male mice 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 with 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 bone remodeling. In conclusion, OMD is a key factor in subchondral bone sclerosis associated with OA. It participates in bone and cartilage homeostasis by acting on the regulation of osteoclastogenesis. Targeting OMD may be a promising new and personalized approach for OA.
