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Blockade of receptor‐activated G i signaling in osteoblasts in vivo leads to site‐specific increases in cortical and cancellous bone formation
Author(s) -
Millard Susan M,
Louie Alyssa M,
Wattanachanya Lalita,
Wronski Thomas J,
Conklin Bruce R,
Nissenson Robert A
Publication year - 2011
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.273
Subject(s) - osteoblast , cancellous bone , endocrinology , osteoclast , bone resorption , medicine , cortical bone , chemistry , bone remodeling , receptor , in vivo , osteopenia , microbiology and biotechnology , osteoporosis , biology , anatomy , bone mineral , in vitro , biochemistry
Osteoblasts play a critical role in the maintenance of bone mass through bone formation and regulation of bone resorption. Targeted expression of a constitutively active engineered G i ‐coupled G protein–coupled receptor (GPCR) to osteoblasts in vivo leads to severe osteopenia. However, little is known about the role of endogenous receptor‐mediated G i signaling in regulating osteoblast function. In this study, we investigated the skeletal effects of blocking G i ‐coupled signaling in osteoblasts in vivo. This was accomplished by transgenic expression of the catalytic subunit of pertussis toxin (PTX) under control of the collagen Iα 2.3‐kb promoter. These mice, designated Col1(2.3) + /PTX + , showed increased cortical thickness at the femoral midshaft at 12 weeks of age. This correlated with increased periosteal bone formation associated with expanded mineralizing surface observed in 8‐week‐old mice of both genders. The cancellous bone phenotype of the Col1(2.3) + /PTX + mice was sexually dimorphic, with increases in fractional bone volume at the distal femur seen only in females. Similarly, while cancellous bone‐formation rates were unchanged in males, they could not be quantified for female Col1(2.3) + /PTX + mice owing to the disorganized nature of the labeling pattern, which was consistent with rapid formation of woven bone. Alterations in osteoclast activity did not appear to participate in the phenotype. These data demonstrate that G i ‐coupled signaling by GPCRs endogenous to osteoblasts plays a complex role in the regulation of bone formation in a manner that is dependent on both gender and the anatomic site within bone. © 2011 American Society for Bone and Mineral Research.