title: The in vivo role of DMP-1 and serum phosphate on bone mineral composition.
abstract: Human DMP1 mutations or Dmp1-null (KO) mice display hypophosphatemia rickets, suggesting a causative role of low phosphate (P) in development of osteomalacia. To address the direct contribution of P to the in vivo bone mineralization we analyzed the properties of femurs obtained from Dmp1 null mice and wild type (WT) mice under a normal or high phosphorous (HiP) diet using combined assays, including histological examination, micro computed tomography (μCT), X-ray absorption near edge structure (XANES) spectroscopy and Raman spectroscopy. Histology and XANES indicate that WT mice have phosphate coordinated with Ca in the form of hydroxyapatite and tricalcium phosphate, while the KO mice have poorly coordinated soluble phosphates in their structure in both the normal and HiP diets. Raman spectroscopy and XANES indicate a higher carbonate/phosphate ratio and a low mineral/matrix ratio in the osteoid clusters in the KO femurs, which was only partially improved by HiP diets. Thus, we conclude that the hypophosphatemia induced osteomalacia phenotype in Dmp1 KO mice is contributed by at least two factors: the low Pi level and the DMP1 local function in mineralization.
authors: Materials Science and Engineering Department, University of Texas at Arlington, Arlington, TX 76019, United States.
authors: Megen
authors: M
authors: Maginot
authors: Department of Biomedical Sciences, Texas A&M Health Science Center, Baylor College of Dentistry, Dallas TX 75246, United States.
authors: Shuxian
authors: S
authors: Lin
authors: Department of Biomedical Sciences, Texas A&M Health Science Center, Baylor College of Dentistry, Dallas TX 75246, United States.
authors: Ying
authors: Y
authors: Liu
authors: School of Medicine and Public Health, Univ. Wisconsin, Madison, WI 53715, United States.
authors: Baozhi
authors: B
authors: Yuan
authors: Department of Biomedical Sciences, Texas A&M Health Science Center, Baylor College of Dentistry, Dallas TX 75246, United States.
authors: Jian Q
authors: JQ
authors: Feng
authors: Materials Science and Engineering Department, University of Texas at Arlington, Arlington, TX 76019, United States. Electronic address: Aswath@uta.edu.
authors: Pranesh B
authors: PB
authors: Aswath
mesh_terms: D000818:Animals; D015519:Bone Density / Q000502:physiology*; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005269:Femur / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008855:Microscopy, Electron, Scanning; D010018:Osteomalacia / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D010710:Phosphates / Q000008:administration & dosage / Q000097:blood*; D063730:Rickets, Hypophosphatemic / Q000150:complications / Q000378:metabolism / Q000473:pathology; D013059:Spectrum Analysis, Raman; D055114:X-Ray Microtomography
chemical_list: C513308:Dmp1 protein, mouse; D016326:Extracellular Matrix Proteins; D010710:Phosphates