Unique roles of phosphorus in endochondral bone formation and osteocyte maturation |
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| Authors: | 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 |
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| Affiliation: | 1. Department of Operative Dentistry and Endodontics, School of Stomatology, Fourth Military Medical University, Xi'an, People's Republic of China;2. Biomedical Sciences, Baylor College of Dentistry, Texas A&M Health Science Center, Dallas, TX, USA;3. Oral Biology, University of Missouri–Kansas City, Kansas City, MO, USA;4. Department of Medicine, University of Wisconsin and GRECC, VA Medical Center, Madison, WI, USA |
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| 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. © 2011 American Society for Bone and Mineral Research. |
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| Keywords: | DMP‐1 HYPOPHOSPHATEMIC RICKETS FGF‐23 PHOSPHATE HOMEOSTASIS OSTEOCYTE |
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