Osteoclast-Derived Complement Component 3a Stimulates Osteoblast Differentiation
Osteoclast-Derived Complement Component 3a Stimulates Osteoblast Differentiation
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DOI：
10.1002/jbmr.2187
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发表时间：
2014-07-01
影响因子：
6.2
通讯作者：
Takeshita, Sunao
中科院分区：
文献类型：
--
作者：
Matsuoka, Kazuhiko;Park, Kyoung-ae;Takeshita, Sunao
骨重建是通过骨吸收与骨形成的耦合来调节的，然而，“耦合因子”和潜在的机制还不完全清楚。在这里，我们发现，条件培养基（CM）的成熟破骨细胞含有一种体液因子，刺激分化的主要成骨细胞，碱性磷酸酶（ALP）活性测定。我们纯化成骨细胞生成刺激活性从3 L的破骨细胞CM通过连续的离子交换色谱监测成骨细胞的ALP活性，并确定补体成分3（C3）。破骨细胞生成过程中C3基因的表达增加，ELISA检测到破骨细胞CM中的裂解产物C3 a，但骨髓巨噬细胞中未检测到。破骨细胞CM中存在的成骨细胞生成刺激活性被C3 a受体（C3 aR）的特异性拮抗剂SB 290157抑制。相反，C3 a的逆转录病毒表达以及用C3 aR激动剂苯乙酰胺治疗刺激成骨细胞分化。骨中C3基因表达在卵巢切除术（OVX）或注射NF-κ B配体受体激活剂（RANKL）的高骨转换状态下增加，并且通过每日施用SB 290157来阻断C3 a的作用导致OVX所升高的骨形成的衰减和骨丢失的加剧。这些结果表明，破骨细胞衍生的C3 a功能的继电器从骨吸收形成，并可能是一个耦合因子的候选人。(C)2014年美国骨与矿物质研究学会。
Bone remodeling is regulated by a coupling of resorption to subsequent formation; however, the "coupling factor" and underlying mechanism are not fully understood. Here, we found that the condition medium (CM) of mature osteoclasts contains a humoral factor that stimulates the differentiation of primary osteoblasts, as determined by alkaline phosphatase (ALP) activity. We purified osteoblastogenesis-stimulating activity from 3 L of osteoclast CM through successive ion exchange chromatographies by monitoring the ALP activity of osteoblasts and identified complement component 3 (C3). Expression of the C3 gene increased during osteoclastogenesis, and the cleavage product C3a was detected by ELISA in the CM of osteoclasts but not in that of bone marrow macrophages. The osteoblastogenesis-stimulating activity present in osteoclast CM was inhibited by a specific antagonist of the C3a receptor (C3aR), SB290157. Conversely, the retroviral expression of C3a as well as treatment with the C3aR agonist, benzeneacetamide, stimulated osteoblast differentiation. C3 gene expression in bone was increased in the high bone turnover states of ovariectomy (OVX) or a receptor activator of NF-kappa B ligand (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. (C) 2014 American Society for Bone and Mineral Research.