Mineral composition is altered by osteoblast expression of an engineered G(s)-coupled receptor.

Autor:	Kazakia, G., Speer, D., Shanbhag, S., Majumdar, S., Conklin, B., Nissenson, R., Hsiao, E., Kazakia, G J, Conklin, B R, Nissenson, R A, Hsiao, E C
Předmět:	MINERAL metabolism GENE expression CELL receptors FOURIER transform infrared spectroscopy TOMOGRAPHY FIBROUS dysplasia of bone TRANSGENIC mice BIOMINERALIZATION BONE metabolism OSTEOBLAST metabolism ANIMAL experimentation BONES CELLULAR signal transduction COMPARATIVE studies COMPUTED tomography FEMUR INFRARED spectroscopy RESEARCH methodology MEDICAL cooperation MEMBRANE proteins MICE PARTICLE accelerators RESEARCH RESEARCH funding EVALUATION research BONE density
Zdroj:	Calcified Tissue International; Jul2011, Vol. 89 Issue 1, p10-20, 11p, 1 Color Photograph, 2 Black and White Photographs, 2 Charts, 3 Graphs
Abstrakt:	Activation of the G(s) G protein-coupled receptor Rs1 in osteoblasts increases bone mineral density by 5- to 15-fold in mice and recapitulates histologic aspects of fibrous dysplasia of the bone. However, the effects of constitutive G(s) signaling on bone tissue quality are not known. The goal of this study was to determine bone tissue quality in mice resulting from osteoblast-specific constitutive G(s) activation, by the complementary techniques of FTIR spectroscopy and synchrotron radiation micro-computed tomography (SRμCT). Col1(2.3)-tTA/TetO-Rs1 double transgenic (DT) mice, which showed osteoblast-specific constitutive G(s) signaling activity by the Rs1 receptor, were created. Femora and calvariae of DT and wild-type (WT) mice (6 and 15 weeks old) were analyzed by FTIR spectroscopy. WT and DT femora (3 and 9 weeks old) were imaged by SRμCT. Mineral-to-matrix ratio was 25% lower (P = 0.010), carbonate-to-phosphate ratio was 20% higher (P = 0.025), crystallinity was 4% lower (P = 0.004), and cross-link ratio was 11% lower (P = 0.025) in 6-week DT bone. Differences persisted in 15-week animals. Quantitative SRμCT analysis revealed substantial differences in mean values and heterogeneity of tissue mineral density (TMD). TMD values were 1,156 ± 100 and 711 ± 251 mg/cm(3) (mean ± SD) in WT and DT femoral diaphyses, respectively, at 3 weeks. Similar differences were found in 9-week animals. These results demonstrate that continuous G(s) activation in murine osteoblasts leads to deposition of immature bone tissue with reduced mineralization. Our findings suggest that bone tissue quality may be an important contributor to increased fracture risk in fibrous dysplasia patients. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
Externí odkaz:	Zobrazit plný text záznamu Full text from SpringerLink