Year: 2010
Type: article
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.
DOI: 10.1002/jbmr.294
Language: English
Topic: Bone Metabolism and Diseases
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Awards: G1747574694, G1867541323, A Critical Role of DMP-1 in Mineralization, G3234645251, PATHOGENESIS OF VITAMIN D REFRACTORY DISEASES, DMP1 Mutations: Defects in Odontogenesis, Studies of the Roles of DMP1 and DSPP in Osteogenesis and Dentinogenesis, Osteocyte Function and Effects of Mechanical Strain, G7023509590, G9000202607
OpenAlex ID: W1994611947