title: Unique roles of phosphorus in endochondral bone formation and osteocyte maturation.
abstract: The mechanisms by which inorganic phosphate (P(i)) 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 P(i) 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.
authors.affiliation: Department of Operative Dentistry and Endodontics, School of Stomatology, Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.forename: Yongbo
authors.initials: Y
authors.lastname: Lu
authors.forename: Ling
authors.initials: L
authors.lastname: Ye
authors.forename: Baozhi
authors.initials: B
authors.lastname: Yuan
authors.forename: Shibin
authors.initials: S
authors.lastname: Yu
authors.forename: Chunlin
authors.initials: C
authors.lastname: Qin
authors.forename: Yixia
authors.initials: Y
authors.lastname: Xie
authors.forename: Tian
authors.initials: T
authors.lastname: Gao
authors.forename: Marc K
authors.initials: MK
authors.lastname: Drezner
authors.forename: Lynda F
authors.initials: LF
authors.lastname: Bonewald
authors.forename: Jian Q
authors.initials: JQ
authors.lastname: Feng
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D016723:Bone Remodeling / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D016326:Extracellular Matrix Proteins / Q000172:deficiency; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000276:immunology; D006706:Homeostasis / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010011:Osteocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D010710:Phosphates / Q000378:metabolism; D010758:Phosphorus / Q000378:metabolism*
chemical_list: D000906:Antibodies; D015415:Biomarkers; C513308:Dmp1 protein, mouse; D016326:Extracellular Matrix Proteins; C000717428:Fgf23 protein, mouse; D010710:Phosphates; D010758:Phosphorus; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23