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首页> 外文期刊>Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research >The Type I BMP Receptor ACVR1/ALK2 is Required for Chondrogenesis During Development
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The Type I BMP Receptor ACVR1/ALK2 is Required for Chondrogenesis During Development

机译：I型BMP受体ACVR1 / ALK2是发育过程中软骨形成所必需的

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Bone morphogenetic proteins (BMPs) are crucial regulators of chondrogenesis. BMPs transduce their signals through three type I receptors: BMPR1A, BMPR1B, and ACVR1/ALK2. Fibrodysplasia ossificans progressiva (FOP), a rare disorder characterized by progressive ossification of connective tissue, is caused by an activating mutation in Acvr1 (the gene that encodes ACVR1/ALK2). However, there are few developmental defects associated with FOP. Thus, the role of ACVR1 in chondrogenesis during development is unknown. Here we report the phenotype of mice lacking ACVR1 in cartilage. Acvr1(CKO) mice are viable but exhibit defects in the development of cranial and axial structures. Mutants exhibit a shortened cranial base, and cervical vertebrae are hypoplastic. Acvr1(CKO) adult mice develop progressive kyphosis. These morphological defects were associated with decreased levels of Smad1/5 and p38 activation, and with reduced rates of chondrocyte proliferation in vertebral cartilage. We also tested whether ACVR1 exerts coordinated functions with BMPR1A and BMPR1B through analysis of double mutants. Acvr1/Bmpr1a and Acvr1/Bmpr1b mutant mice exhibited generalized perinatal lethal chondrodysplasia that was much more severe than in any of the corresponding mutant strains. These findings demonstrate that ACVR1 is required for chondrocyte proliferation and differentiation, particularly in craniofacial and axial elements, but exerts coordinated functions with both BMPR1A and BMPR1B throughout the developing endochondral skeleton. (c) 2014 American Society for Bone and Mineral Research.
机译：骨形态发生蛋白（BMP）是软骨形成的关键调节因子。 BMP通过三种I型受体转导信号：BMPR1A，BMPR1B和ACVR1 / ALK2。骨增生性纤维增生症（FOP）是一种罕见疾病，特征是结缔组织逐渐骨化，是由Acvr1（编码ACVR1 / ALK2的基因）的激活性突变引起的。但是，很少有与FOP相关的发育缺陷。因此，未知ACVR1在发育过程中在软骨形成中的作用。在这里，我们报告小鼠缺乏软骨中ACVR1的表型。 Acvr1（CKO）小鼠是可行的，但在颅骨和轴结构的发育中表现出缺陷。突变体的颅底变短，颈椎发育不良。 Acvr1（CKO）成年小鼠发展为进行性驼背。这些形态缺陷与Smad1 / 5和p38激活水平降低以及椎软骨软骨细胞增殖速率降低有关。我们还通过双重突变体分析测试了ACVR1是否与BMPR1A和BMPR1B发挥协调功能。 Acvr1 / Bmpr1a和Acvr1 / Bmpr1b突变小鼠表现出普遍的围产期致死软骨发育不良，其严重性远高于任何相应的突变株。这些发现表明，ACVR1是软骨细胞增殖和分化所必需的，尤其是在颅面和轴向元素中，但是在整个发育中的软骨内骨架中，与BMPR1A和BMPR1B都起着协调的作用。 （c）2014年美国骨矿物质研究学会。

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