Unique roles of phosphorus in endochondral bone formation and osteocyte maturation

Rong Zhang, Yongbo Lu, Ling Ye, Baozhi Yuan, Shibin Yu, Chunlin Qin, Yixia Xie, Tian Gao, Marc K. Drezner, Lynda F. Bonewald, Jian Q. Feng

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

The mechanisms by which inorganic phosphate (Pi) homeostasis controls bone biology are poorly understood. Here we used Dmp1 null mice, a hypophosphatemic rickets/osteomalacia model, combined with a metatarsal organ culture and an application of neutralizing fibroblast growth factor 23 (FGF-23) antibodies to gain insight into the roles of Pi in bone biology. We showed (1) that abnormal bone remodeling in Dmp1 null mice is due to reduced osteoclast number, which is secondary to a reduced ratio of RANKL/OPG expressed by osteoclast supporting cells and (2) that osteoblast extracellular matrix mineralization, growth plate maturation, secondary ossification center formation, and osteoblast differentiation are phosphate-dependent. Finally, a working hypothesis is proposed to explain how phosphate and DMP1 control osteocyte maturation.

Original languageEnglish (US)
Pages (from-to)1047-1056
Number of pages10
JournalJournal of Bone and Mineral Research
Volume26
Issue number5
DOIs
StatePublished - May 1 2011

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Keywords

  • DMP-1
  • FGF-23
  • HYPOPHOSPHATEMIC RICKETS
  • OSTEOCYTE
  • PHOSPHATE HOMEOSTASIS

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

Cite this

Zhang, R., Lu, Y., Ye, L., Yuan, B., Yu, S., Qin, C., Xie, Y., Gao, T., Drezner, M. K., Bonewald, L. F., & Feng, J. Q. (2011). Unique roles of phosphorus in endochondral bone formation and osteocyte maturation. Journal of Bone and Mineral Research, 26(5), 1047-1056. https://doi.org/10.1002/jbmr.294