Collagens VI and XII form complexes mediating osteoblast interactions during osteogenesis.
Collagens VI and XII form complexes mediating osteoblast interactions during osteogenesis.
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DOI：
10.1007/s00441-015-2345-y
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发表时间：
2016-06
影响因子：
3.6
通讯作者：
Noda M
中科院分区：
文献类型：
--
作者：
Izu Y;Ezura Y;Koch M;Birk DE;Noda M
成骨细胞中的细胞间通讯精确地调控骨的形成。我们之前已经证明，Col6a1或Col12a1的基因缺失会损害小鼠成骨细胞的连接和/或通讯，导致骨量减少和骨脆性。编码VI型胶原的基因突变会导致Ullrich先天性肌营养不良症(UCMD)和Bethlem肌病(BM)，这两种疾病的表型重叠，涉及结缔组织和肌肉。最近的研究发现，在UCMD和BM样疾病患者中没有COL6突变的COL12A1基因突变，表明这些胶原蛋白在结缔组织动态平衡中具有共同的功能。本研究的目的是验证第六型和第十二型胶原在骨形成过程中具有协同调节作用的假说(S)。我们分析了在成骨过程中，VI型和XII型胶原相对于原代成骨细胞的定位。免疫荧光分析表明，在成骨细胞建立细胞-细胞连接的过程中，VI和XII胶原共存于相邻细胞之间的基质桥中。对含有胶原桥的细胞的定量检测表明，基质桥由VI和XII胶原组成，而不是I型胶原。有趣的是，缺乏Col6a1或Col12a1的成骨细胞基质桥的形成受到损害，这表明这两种胶原是基质桥形成所必需的。这些数据首次证明了在成骨过程中VI和XII胶原之间的功能关系，并表明在骨形成过程中，包含VI和XII胶原的复合体对于形成沟通的细胞网络是必不可少的。本文的在线版本(doi：10.1007/s00441-0152345-y)包含补充材料，授权用户可以使用。
Bone formation is precisely regulated by cell-cell communication in osteoblasts. We have previously demonstrated that genetic deletion of Col6a1 or Col12a1 impairs osteoblast connections and/or communication in mice, resulting in bone mass reduction and bone fragility. Mutations of the genes encoding collagen VI cause Ullrich congenital muscular dystrophy (UCMD) and Bethlem myopathy (BM), which have overlapping phenotypes involving connective tissue and muscle. Recent studies have identified COL12A1 gene mutations in patients with UCMD- and BM-like disorders harboring no COL6 mutations, indicating the shared functions of these collagens in connective tissue homeostasis. The purpose of this investigation has been to test the hypothesis that collagens VI and XII have coordinate regulatory role(s) during bone formation. We analyzed the localization of collagens VI and XII relative to primary osteoblasts during osteogenesis. Immunofluorescence analysis demonstrated that collagens VI and XII colocalized in matrix bridges between adjacent cells during periods when osteoblasts were establishing cell-cell connections. Quantification of cells harboring collagen bridges demonstrated that matrix bridges were composed of collagens VI and XII but not collagen I. Interestingly, matrix bridge formation was impaired in osteoblasts deficient in either Col6a1 or Col12a1, suggesting that both collagens were indispensable for matrix bridge formation. These data demonstrate, for the first time, a functional relationship between collagens VI and XII during osteogenesis and indicate that a complex containing collagens VI and XII is essential for the formation of a communicating cellular network during bone formation. The online version of this article (doi:10.1007/s00441-015-2345-y) contains supplementary material, which is available to authorized users.