软骨内成骨过程中软骨基质降解和矿化是影响长骨的生长，但其中的机制一直未被阐明。破骨细胞是参与基质降解的主要细胞，破骨细胞缺陷会导致生长板异常从而影响骨的正常发育，因此探明破骨细胞在骨发育中尤其是软骨内成骨中的作用有着重要的研究价值。前期研究我们发现破骨细胞敲除raptor的小鼠具有整体短小的侏儒表现，对生长板进行检测发现敲除小鼠生长板肥大软骨区变窄、软骨基质减少。此外，骨缺损动物模型证实软骨内成骨过程在敲除小鼠中受到明显抑制。同时，通过蛋白组学筛选，发现raptor敲除的破骨细胞其S100A9蛋白表达显著减少。因此，本项目拟从分子、细胞和整体水平探讨破骨细胞来源的S100A9介导破骨-软骨细胞相互作用，及其对软骨内成骨的影响，并尝试阐明其中的分子机制，为软骨内成骨的调控增添新的理论基础。

The cartilage matrix degradation and mineralization during endochondral ossification determine the development of long bone. However, the mechanism has not been elucidated. The resorb function of osteoclast plays an important role in bone development, the defects of osteoclast can lead to abnormal growth plate and affect the normal development of bone. It is of great importance to explore the role of osteoclasts in bone development, especially in the process of endochondral ossification.. We previously found that the mice with specific knockout of raptor in osteoclasts showed constricted growth plate and short overall dwarf dysplasia. What’s more, the Drill-hole injury animal model confirmed that the endochondral osteogenesis was significantly inhibited in the knockout mice. Through the screening of proteomics, we found the expression of S100A9 protein in raptor knockout osteoclasts was significantly reduced.. In this proposal, we aim to further study the function and mechanistic regulation of S100A9 expression in osteoclast, in addition, the role and molecular mechanisms of osteoclastic Rps18 acting on chondrocytes in bone development, especially in endochondral ossification need to be explored and clarified.