The biological function of DMP-1 in osteocyte maturation is mediated by its 57-kDa C-terminal fragment.
The biological function of DMP-1 in osteocyte maturation is mediated by its 57-kDa C-terminal fragment.
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DOI：
10.1002/jbmr.226
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发表时间：
2011-02
影响因子：
6.2
通讯作者：
Feng, Jian Q.
中科院分区：
文献类型：
--
作者：
Lu, Yongbo;Yuan, Baozhi;Qin, Chunlin;Cao, Zhengguo;Xie, Yixia;Dallas, Sarah L.;McKee, Marc D.;Drezner, Marc K.;Bonewald, Lynda F.;Feng, Jian Q.
牙本质基质蛋白-1(DMP-1)是控制骨细胞形成和磷酸盐稳态的关键分子。根据在骨骼中没有发现全长DMP-1，而只存在37和57 kDa的切割片段的观察，以及鉴于57 kDa片段的突变导致疾病的发现，我们假设57 kDa的C末端片段是DMP-1的功能结构域。为了验证这一假设，我们使用3.6kb的I型胶原启动子来表达这个57 kDa的C末端片段，并将其与Dmp1缺失的成骨细胞/骨细胞中的全长DMP-1进行比较。全长DMP-1在骨细胞中的表达不仅完全挽救了DMP1基因缺失小鼠的骨骼异常，而且57 kDa片段也有类似的结果。这包括挽救生长板缺陷、骨软化、异常骨细胞成熟和异常骨细胞陷窝系统。此外，骨细胞中成纤维细胞生长因子23的异常表达、循环中成纤维细胞生长因子23水平的升高和低磷血症也得到了挽救。这些结果表明，57 kDa的C末端片段是DMP-1的功能结构域，控制着骨细胞的成熟和磷酸盐代谢。©2011美国骨与矿物研究学会。
Dentin matrix protein 1 (DMP-1) is a key molecule in controlling osteocyte formation and phosphate homeostasis. Based on observations that full-length DMP-1 is not found in bone, but only cleaved fragments of 37 and 57 kDa are present, and in view of the finding that mutations in the 57-kDa fragment result in disease, we hypothesized that the 57-kDa C-terminal fragment is the functional domain of DMP-1. To test this hypothesis, a 3.6-kb type I collagen promoter was used to express this 57-kDa C-terminal fragment for comparison with full-length DMP-1 in Dmp1 null osteoblasts/osteocytes. Not only did expression of the full-length DMP-1 in bone cells fully rescue the skeletal abnormalities of Dmp1 null mice, but the 57-kDa fragment also had similar results. This included rescue of growth plate defects, osteomalacia, abnormal osteocyte maturation, and the abnormal osteocyte lacunocanalicular system. In addition, the abnormal fibroblast growth factor 23 (FGF-23) expression in osteocytes, elevated circulating FGF-23 levels, and hypophosphatemia were rescued. These results show that the 57-kDa C-terminal fragment is the functional domain of DMP-1 that controls osteocyte maturation and phosphate metabolism. © 2011 American Society for Bone and Mineral Research.
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