Identification and characterization of osteoclast-derived coupling factor

骨重建是通过吸收与后续形成的耦合来调节的，然而，“耦合因子”及其潜在的机制还不完全清楚。我通过连续层析从破骨细胞CM中纯化了成骨细胞刺激活性，通过检测ALP活性来确定其活性，并鉴定了补体成分3(C3)。破骨细胞CM的活性可被C3a受体拮抗剂SB290157抑制。在去卵巢或注射RANKL的高骨转换状态下，C3基因在骨组织中的表达增加，每日给予SB290157阻断C3a的作用，可抑制OVX促进的骨形成，加重骨丢失。这些结果表明，破骨细胞来源的C3a在骨吸收到骨形成的过程中发挥作用，可能是一种偶联因子。

Bone remodeling is regulated by a coupling of resorption to subsequent formation, however, the "coupling factor" and underlying mechanism are not fully understood. I purified osteoblast-stimulating activity, as determined by ALP activity, from osteoclast CM through successive chromatography by monitoring the ALP activity, and identified complement component 3 (C3). The activity present in osteoclast CM was inhibited by a specific C3a receptor antagonist, SB290157. C3 gene expression in bone was increased in the high bone turnover states of ovariectomy (OVX) or a RANKL injection, and blocking the action of C3a with the daily administration of SB290157 resulted in the attenuation of bone formation elevated by OVX, and the exacerbation of bone loss. These results suggest that osteoclast-derived C3a functions in the relay from bone resorption to formation and may be a candidate for a coupling factor.