Deletion of BMP receptor type IB decreased bone mass in association with compromised osteoblastic differentiation of bone marrow mesenchymal progenitors.
Deletion of BMP receptor type IB decreased bone mass in association with compromised osteoblastic differentiation of bone marrow mesenchymal progenitors.
复制标题
IB型BMP受体的缺失导致骨量减少，这与骨髓间充质祖细胞的成骨细胞分化受损有关
DOI：
10.1038/srep24256
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发表时间：
2016-04-06
影响因子：
4.6
通讯作者：
Sun H
中科院分区：
文献类型：
--
作者：
Shi C;Iura A;Terajima M;Liu F;Lyons K;Pan H;Zhang H;Yamauchi M;Mishina Y;Sun H
我们以前发现，破坏两个I型BMP受体，Bmpr 1a和Acvr 1，分别以成骨细胞特异性的方式，增加小鼠的骨量。BMPR 1B是另一种BMP I型受体，也能够结合BMP配体并抑制BMP信号传导。然而，对BMPR 1B在骨中的功能知之甚少。在这项研究中，我们研究了Bmpr 1b基因敲除小鼠的骨表型以及Bmpr 1b基因敲除对成骨细胞和破骨细胞的影响。我们发现Bmpr 1b基因的缺失导致8周龄雄性小鼠的骨质减少，并且表型是暂时的和性别特异性的。骨量减少既不是体内成骨细胞骨形成活性的改变，也不是体内成骨细胞骨吸收活性的改变。在体外Bmpr 1b null破骨细胞的分化增加，但吸收活性下降。Bmpr 1b突变体的颅骨前成骨细胞在体外表现出相当的分化能力，而在培养中表现出BMP-SMAD信号增强。与颅骨前成骨细胞不同，Bmpr 1b突变小鼠骨髓间充质祖细胞在体外表现出分化障碍，这可能是Bmpr 1b突变小鼠成骨表型减少的原因之一。总之，我们的结果表明BMPR 1B在维持骨量和转导BMP信号方面发挥着与BMPR 1A和ACVR 1不同的作用。
We previously found that disruption of two type I BMP receptors,Bmpr1aandAcvr1, respectively, in an osteoblast-specific manner, increased bone mass in mice. BMPR1B, another BMP type I receptor, is also capable of binding to BMP ligands and transduce BMP signaling. However, little is known about the function of BMPR1B in bone. In this study, we investigated the bone phenotype inBmpr1bnull mice and the impacts of loss ofBmpr1bon osteoblasts and osteoclasts. We found that deletion ofBmpr1bresulted in osteopenia in 8-week-old male mice and the phenotype was transient and gender specific. The decreased bone mass was neither due to the changes in osteoblastic bone formation activity nor osteoclastic bone resorption activityin vivo. In vitrodifferentiation ofBmpr1bnull osteoclasts was increased but resorption activity was decreased. Calvarial pre-osteoblasts fromBmpr1bmutant showed comparable differentiation capabilityin vitro, while they showed increased BMP-SMAD signaling in culture. Different from calvarial pre-osteoblasts,Bmpr1bmutant bone marrow mesenchymal progenitors showed compromised differentiationin vitro, which may be a reason for the osteopenic phenotype in the mutant mice. In conclusion, our results suggested that BMPR1B plays distinct roles from BMPR1A and ACVR1 in maintaining bone mass and transducing BMP signaling.