Bone morphogenic protein 2 directly enhances differentiation of murine osteoclast precursors.
Bone morphogenic protein 2 directly enhances differentiation of murine osteoclast precursors.
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DOI：
10.1002/jcb.22462
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发表时间：
2010-03-01
影响因子：
4
通讯作者：
Mansky, Kim
中科院分区：
文献类型：
--
作者：
Jensen, Eric D.;Pham, Lan;Billington, Charles J., Jr.;Espe, Kelly;Carlson, Ann E.;Westendorf, Jennifer J.;Petryk, Anna;Gopalakrishnan, Rajaram;Mansky, Kim
以往的研究发现BMP支持破骨细胞的形成，但尚不清楚这是对破骨细胞的直接作用还是通过成骨细胞间接介导的。我们已经表明，一个缺乏BMP拮抗剂扭曲原肠胚形成的小鼠，骨形态发生蛋白对破骨细胞生成的直接积极作用。在这份报告中，我们进一步确定BMP信号转导对体外破骨细胞形成的意义。我们发现BMP 2与次优水平的RANKL协同增强破骨细胞样细胞的体外分化。BMP 2的增强不是骨髓衍生培养物的增殖或存活率变化的结果，而是伴随着参与破骨细胞分化和融合的基因表达的增加。在我们的破骨细胞培养物中，BMP 2处理没有显著改变RANKL或OPG的表达，这表明破骨细胞生成的增强不是通过成骨细胞或基质细胞间接介导的。与此一致，我们检测到磷酸化SMAD 1，5，8（p-SMAD）的单核细胞和多核细胞的破骨细胞培养物的细胞核。在分化过程中，p-SMAD、BMP 2和BMP受体的水平增加。II型BMP受体的RNA干扰抑制抑制RANKL刺激的多核TRAP阳性细胞的形成。当在第3天之前加入时，BMP拮抗剂头蛋白抑制RANKL介导的破骨细胞分化，而在第3天或之后加入头蛋白未能抑制其分化。总之，这些数据表明，破骨细胞表达BMP 2和BMP受体，自分泌BMP信号直接促进破骨细胞样细胞的分化。
Previous studies found that BMPs support osteoclast formation, but it is not clear whether this is a direct effect on osteoclasts or mediated indirectly through osteoblasts. We have shown that a mouse deficient for the BMP antagonist Twisted gastrulation suggested a direct positive role for BMPs on osteoclastogenesis. In this report, we further determine the significance of BMP signaling on osteoclast formation in vitro. We find that BMP2 synergizes with suboptimal levels of RANKL to enhance in vitro differentiation of osteoclast-like cells. The enhancement by BMP2 is not a result of changes in the rate of proliferation or survival of the bone marrow derived cultures, but is accompanied by an increase in expression of genes involved in osteoclast differentiation and fusion. Treatment with BMP2 did not significantly alter expression of RANKL or OPG in our osteoclast cultures, suggesting that the enhancement of osteoclastogenesis is not mediated indirectly through osteoblasts or stromal cells. Consistent with this, we detected phosphorylated SMAD1,5,8 (p-SMAD) in the nuclei of mononuclear and multinucleated cells in osteoclast cultures. Levels of p-SMAD, BMP2 and BMP receptors increased during differentiation. RNAi suppression of Type II BMP receptor inhibited RANKL-stimulated formation of multinuclear TRAP positive cells. The BMP antagonist noggin inhibited RANKL-mediated osteoclast differentiation when added prior to day 3, while addition of noggin on day 3 or later failed to inhibit their differentiation. Taken together, these data indicate that osteoclasts express BMP2 and BMP receptors, and that autocrine BMP signaling directly promotes the differentiation of osteoclasts-like cells.
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影响因子：
6.2
作者：
Okamoto, Mina;Murai, Junko;Tsumaki, Noriyuki
通讯作者：
Tsumaki, Noriyuki
影响因子：
4.1
作者：
Komarova, SV;Smith, RJ;Wahl, LM
通讯作者：
Wahl, LM
影响因子：
11.5
作者：
Guise, Theresa A.;Mohammad, Khalid S.;Chirgwin, John M.
通讯作者：
Chirgwin, John M.
影响因子：
6.2
作者：
Abe, E;Yamamoto, M;Manolagas, SC
通讯作者：
Manolagas, SC
影响因子：
6.2
作者：
KANATANI, M;SUGIMOTO, T;CHIHARA, K
通讯作者：
CHIHARA, K