Parathyroid hormone stimulates osteoblastic expression of MCP-1 to recruit and increase the fusion of pre/osteoclasts
Parathyroid hormone stimulates osteoblastic expression of MCP-1 to recruit and increase the fusion of pre/osteoclasts
复制标题
DOI：
10.1074/jbc.m611781200
复制
发表时间：
2007-11-09
影响因子：
4.8
通讯作者：
Partridge, Nicola C.
中科院分区：
文献类型：
--
作者：
Li, Xin;Qin, Ling;Partridge, Nicola C.
阿仑膦酸钠减弱人甲状旁腺激素（PTH）对骨形成的合成代谢作用的临床研究结果表明，主动吸收参与并增强了合成代谢作用。PTH通过其在成骨细胞膜上的受体发出信号，破骨细胞通过成骨细胞的产物间接受到影响。来自注射人PTH或载体的大鼠的RNA微阵列显示单核细胞趋化蛋白-1（MCP-1）的刺激与PTH的合成代谢作用之间存在强烈的关联。在每天注射PTH的大鼠股骨或原代成骨细胞和UMR 106-01细胞中，PTH快速且显著地刺激MCP-1 mRNA。MCP-1 mRNA的刺激是剂量依赖性的，并且是体外通过cAMP依赖性蛋白激酶途径对PTH信号传导的主要反应。用小鼠单核细胞系RAW 264.7和小鼠骨髓进行的研究证明，成骨细胞MCP-1可以有效地募集破骨细胞单核细胞前体，并促进NF-κ B配体诱导的破骨细胞生成的受体激活剂，特别是增强融合。我们的模型表明，PTH诱导的MCP-1成骨细胞表达参与招募和分化阶段的破骨细胞前体的多核。该信息为PTH合成代谢作用中破骨细胞活性增加以及NF-κ B配体刺激的受体激活剂引发更大的骨重建提供了理论基础。
The clinical findings that alendronate blunted the anabolic effect of human parathyroid hormone ( PTH) on bone formation suggest that active resorption is involved and enhances the anabolic effect. PTH signals via its receptor on the osteoblast membrane, and osteoclasts are impacted indirectly via the products of osteoblasts. Microarray with RNA from rats injected with human PTH or vehicle showed a strong association between the stimulation of monocyte chemoattractant protein-1 ( MCP-1) and the anabolic effects of PTH. PTH rapidly and dramatically stimulated MCP-1 mRNA in the femora of rats receiving daily injections of PTH or in primary osteoblastic and UMR 106-01 cells. The stimulation of MCP-1 mRNA was dose-dependent and a primary response to PTH signaling via the cAMP-dependent protein kinase pathway in vitro. Studies with the mouse monocyte cell line RAW 264.7 and mouse bone marrow proved that osteoblastic MCP-1 can potently recruit osteoclast monocyte precursors and facilitate receptor activator of NF-kappa B ligand-induced osteoclastogenesis and, in particular, enhanced fusion. Our model suggests that PTH-induced osteoblastic expression of MCP-1 is involved in recruitment and differentiation at the stage of multinucleation of osteoclast precursors. This information provides a rationale for increased osteoclast activity in the anabolic effects of PTH in addition to receptor activator of NF-kappa B ligand stimulation to initiate greater bone remodeling.