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The biological function of DMP‐1 in osteocyte maturation is mediated by its 57‐kDa c‐terminal fragment
Author(s) -
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
Publication year - 2011
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.226
Subject(s) - osteocyte , dmp1 , phex , chemistry , osteomalacia , fibroblast growth factor 23 , microbiology and biotechnology , biology , endocrinology , medicine , biochemistry , osteoblast , gene , viral matrix protein , rickets , osteoporosis , calcium , parathyroid hormone , organic chemistry , vitamin d and neurology , in vitro
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.