Bone morphogenetic protein signaling through ACVR1 and BMPR1A negatively regulates bone mass along with alterations in bone composition.

Bone morphogenetic protein signaling through ACVR1 and BMPR1A negatively regulates bone mass along with alterations in bone composition.
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通过 ACVR1 和 BMPR1A 的骨形态发生蛋白信号传导负向调节骨量以及骨成分的改变

DOI:
10.1016/j.jsb.2017.11.010
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发表时间:
2018-03
影响因子:
3
通讯作者:
Sun H
Sun H
中科院分区:
生物学3区
文献类型:
--
作者:
Shi C;Mandair GS;Zhang H;Vanrenterghem GG;Ridella R;Takahashi A;Zhang Y;Kohn DH;Morris MD;Mishina Y;Sun H

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骨量和骨质量是决定骨的性质和力学功能的重要因素。本研究检测了通过BMP受体阻断骨形态发生蛋白(BMP)信号传导对骨量和骨质量的影响。更具体地说,我们破坏了两个BMP受体,Acvr 1和Bmpr 1a,分别在小鼠Osterix表达成骨祖细胞。我们使用显微计算机断层扫描(micro-CT)和组织学检查了3个月大的雄性和雌性条件性基因敲除(cKO)小鼠股骨的结构变化,以及使用拉曼光谱检查了骨皮质和骨小梁室的成分变化。我们发现,Acvr 1和Bmpr 1a的缺失,分别在成骨细胞特异性的方式导致更高的骨小梁间室的骨量。Bmpr 1a的破坏导致骨小梁室中骨量更显著增加。我们还发现,这些cKO小鼠显示出较低的矿物质-基质比,而皮质区室中的组织矿物质密度较低。雄性cKO小鼠的皮质和小梁区室中的胶原交联率较高。我们的研究表明,BMP受体ACVR 1和BMPR 1A介导的成骨细胞中的BMP信号传导在调节骨量和骨质量中至关重要。
Bone quantity and bone quality are important factors in determining the properties and the mechanical functions of bone. This study examined the effects of disrupting bone morphogenetic protein (BMP) signaling through BMP receptors on bone quantity and bone quality. More specifically, we disrupted two BMP receptors, Acvr1 and Bmpr1a, respectively, in Osterix-expressing osteogenic progenitor cells in mice. We examined the structural changes to the femora from 3-month old male and female conditional knockout (cKO) mice using micro-computed tomography (micro-CT) and histology, as well as compositional changes to both cortical and trabecular compartments of bone using Raman spectroscopy. We found that the deletion of Acvr1 and Bmpr1a, respectively, in an osteoblast-specific manner resulted in higher bone mass in the trabecular compartment. Disruption of Bmpr1a resulted in a more significantly increased bone mass in the trabecular compartment. We also found that these cKO mice showed lower mineral-to-matrix ratio, while tissue mineral density was lower in the cortical compartment. Collagen crosslink ratio was higher in both cortical and trabecular compartments of male cKO mice. Our study suggested that BMP signaling in osteoblast mediated by BMP receptors, namely ACVR1 and BMPR1A, is critical in regulating bone quantity and bone quality.
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