TY - JOUR
T1 - Osteomodulin downregulation is associated with osteoarthritis development
AU - Zappia, Jérémie
AU - Tong, Qiao
AU - der Cruyssen, Renée Van
AU - Cornelis, Frederique M. F.
AU - Lambert, Cécile
AU - Coelho, Tiago Pinto
AU - Grisart, Juliane
AU - Kague, Erika
AU - Lories, Rik J.
AU - Muller, Marc
AU - Elewaut, Dirk
AU - Hammond, Chrissy L.
AU - Sanchez, Christelle
AU - Henrotin, Yves
N1 - J.Z., C.L.H., C.S. and Y.H. were responsible for the study design. J.Z. supervised murine in vivo experiments. J.Z. and F.M.F.C. supervised the DMM model. J.Z. and T.P.C. supervised the CatWalk XT experiment. J.Z. and M.M. developed the mutant zebrafish line. J.Z., Q.T., J.G. and E.K. supervised zebrafish in vivo experiments. J.Z. and R.V.d.C. performed the in vitro experiments. J.Z. performed the bone marker assay. J.Z. and C.S. supervised the biomechanical testing. J.Z. wrote the manuscript. R.J.L., M.M., D.E. and C.L.H. provided resources and advised on research studies. C.S. and C.L. advised on research studies. J.Z., C.S. and Y.H. analyzed the results. Y.H. acquired funding, verified data and assisted in writing the manuscript and acts as guarantor. All authors approved the final manuscript.
PY - 2023/9/20
Y1 - 2023/9/20
N2 - 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.
AB - 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.
UR - https://doi.org/10.1038/s41413-023-00286-5
U2 - 10.1038/s41413-023-00286-5
DO - 10.1038/s41413-023-00286-5
M3 - Article
SN - 2095-6231
VL - 11
JO - Bone Research
JF - Bone Research
M1 - 49
ER -