The biological function of DMP-1 in osteocyte maturation is mediated by its 57-kDa c-terminal fragment

Yongbo Lu, Baozhi Yuan, Chunlin Qin, Zhengguo Cao, Yixia Xie, Sarah L. Dallas, Marc D. McKee, Marc K. Drezner, Lynda F. Bonewald, Jian Q. Feng

Research output: Contribution to journalArticle

85 Scopus citations

Abstract

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 57kDa 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.

Original languageEnglish (US)
Pages (from-to)331-340
Number of pages10
JournalJournal of Bone and Mineral Research
Volume26
Issue number2
DOIs
StatePublished - Feb 2011

Keywords

  • DMP-1
  • FGF-23
  • HYPOPHOSPHATEMIC RICKETS
  • MINERALIZATION
  • OSTEOCYTE MATURATION

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

Fingerprint Dive into the research topics of 'The biological function of DMP-1 in osteocyte maturation is mediated by its 57-kDa c-terminal fragment'. Together they form a unique fingerprint.

  • Cite this

    Lu, Y., Yuan, B., Qin, C., Cao, Z., Xie, Y., Dallas, S. L., McKee, M. D., Drezner, M. K., Bonewald, L. F., & Feng, J. Q. (2011). The biological function of DMP-1 in osteocyte maturation is mediated by its 57-kDa c-terminal fragment. Journal of Bone and Mineral Research, 26(2), 331-340. https://doi.org/10.1002/jbmr.226