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.

导致硬化的异常软骨下骨重塑是骨关节炎（OA）的主要特征，骨调节蛋白（OMD）是一种参与细胞外基质矿化的蛋白聚糖，与硬化表型相关。然而，人们对 OMD 的功能仍然知之甚少，特别是在体内。我们使用Omd敲除和过表达的雄性小鼠和突变斑马鱼来研究其在骨和软骨代谢以及 OA 发展中的作用。Omd的表达与骨和软骨微结构密切相关，影响骨量以及软骨下骨硬化和自发性软骨病变的发生。从机制上讲，OMD 与 RANKL 结合并抑制破骨细胞生成，从而控制骨重塑的平衡。总之，OMD 是与 OA 相关的软骨下骨硬化的关键因素。它通过作用于破骨细胞生成的调节来参与骨和软骨的稳态。针对 OMD 可能是一种有前途的新的个性化 OA 方法。