BMP-2 regulation of PTHrP and osteoclastogenic factors during osteoblast differentiation of C2C12 cells
BMP-2 regulation of PTHrP and osteoclastogenic factors during osteoblast differentiation of C2C12 cells
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DOI：
10.1002/jcp.21389
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发表时间：
2008-07-01
影响因子：
5.6
通讯作者：
Ventura, Francesc
中科院分区：
文献类型：
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作者：
Susperregui, Antonio R. G.;Vinals, Francesc;Ventura, Francesc
骨形态发生蛋白-2（BMP-2）强烈参与诱导间充质细胞前体向成骨细胞分化，以及增强成骨细胞产生骨基质。同样地，PTHrP缺陷小鼠的骨质疏松表型清楚地表明了这种旁分泌调节剂在骨生理学中的重要性。在这里，我们报告说，BMP-2迅速下调PTHrP基因的表达，通过转录机制在多能间充质C2 C12细胞，而BMP-2增加PTHrP受体的表达。PTHrP没有显著改变BMP依赖的Smad转录途径。同样，PTHrP没有显著改变BMP调节的RANKL或OPG表达，RANKL或OPG是参与破骨细胞生成的细胞因子。更重要的是，PTHrP的加入，通过PKA信号通路，部分阻止了BMP依赖的诱导C2 C12细胞中的一些成骨标志物，如Runx 2和Osterix。我们的数据表明，BMP-2下调PTHrP可以促进成骨细胞的终末分化。
Bone morphogenetic protein-2 (BMP-2) is strongly involved in the induction of osteoblast differentiation from mesenchymal cell precursors, as well as in enhancing bone matrix production by osteoblastic cells. Likewise, the osteoporotic phenotype of PTHrP deficient mice makes clear the importance of this paracrine regulator in bone physiology. Here, we report that BMP-2 rapidly down-regulated PTHrP gene expression through a transcriptional mechanism in pluripotent mesenchymal C2C12 cells, whereas BMP-2 increased expression of PTHrP receptor. PTHrP did not significantly alter the BMP-dependent Smad transcriptional pathway. Similarly, PTHrP did not significantly modify the BMP-regulated expression of RANKL or OPG, cytokines involved in osteoclastogenesis. More importantly, addition of PTHrP, through the PKA signaling pathway, partially prevented the BMP-dependent induction of some osteogenic markers such as Runx2 and Osterix in C2C12 cells. Our data suggest that BMP-2 down-regulation of PTHrP could facilitate terminal differentiation of osteoblasts.