Department of Endodontics, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
National Clinical Research Center for Oral Diseases, Shanghai, China.
Cell Death Dis. 2021 Feb 1;12(2):147. doi: 10.1038/s41419-021-03404-5.
Osteomodulin (OMD), a member of the small leucine-rich proteoglycan family, distributes in mineralized tissues and is positively regulated by bone morphogenetic protein 2 (BMP2). However, the exact function of OMD during mineralization and its association with BMP2 remain poorly understood. Herein, the expression pattern of OMD during osteogenesis was investigated in human dental pulp stem cells. Silencing OMD gene significantly suppressed the alkaline phosphatase activity, mineralized nodule formation and osteogenesis-associated gene transcription. Besides, OMD could enhance BMP2-induced expression of SP7 and RUNX2 with concentration dependence in vitro. Rat mandibular bone defect model revealed that scaffolds injected with the combination of OMD and suboptimal BMP2 exhibited more mature and abundant mineralized bone than that treated with OMD or suboptimal BMP2 alone. Mechanistically, OMD could bind to BMP2 via its terminal leucine-rich repeats and formed complexes with BMP2 and its membrane receptors, thus promoting BMP/SMAD signal transduction. In addition, OMD was a putative target gene of SMAD4, which plays a pivotal role in this pathway. Collectively, these data elucidate that OMD may act as a positive coordinator in osteogenesis through BMP2/SMADs signaling.
骨钙素（OMD）是小富含亮氨酸的蛋白聚糖家族的成员，分布于矿化组织中，并受骨形态发生蛋白 2（BMP2）的正向调控。然而，OMD 在矿化过程中的确切功能及其与 BMP2 的关联仍知之甚少。本文研究了人牙髓干细胞成骨过程中 OMD 的表达模式。沉默 OMD 基因可显著抑制碱性磷酸酶活性、矿化结节形成和骨形成相关基因转录。此外，OMD 可以体外浓度依赖性地增强 BMP2 诱导的 SP7 和 RUNX2 的表达。大鼠下颌骨缺损模型表明，与单独使用 OMD 或亚最佳浓度 BMP2 相比，与 OMD 和亚最佳浓度 BMP2 联合注射的支架具有更成熟和丰富的矿化骨。在机制上，OMD 可以通过其末端富含亮氨酸的重复序列与 BMP2 及其膜受体形成复合物，从而促进 BMP/SMAD 信号转导。此外，OMD 是 SMAD4 的一个假定靶基因，在该途径中发挥关键作用。总之，这些数据表明 OMD 可能通过 BMP2/SMADs 信号转导在成骨过程中作为一个正协调因子发挥作用。
