期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 105, 期 4, 页码 1209-1214出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0707457105
关键词
RASSL; constitutive G(s) activity; bone formation; cyclic AMP; McCune-Albright syndrome
资金
- NCRR NIH HHS [C06 RR018928, RR18928-01] Funding Source: Medline
- NHLBI NIH HHS [R01 HL060664, R01 HL60664-07] Funding Source: Medline
- NIDDK NIH HHS [R56 DK072071, 2T32DK07418-26, R01 DK072071, T32 DK007418, DK072071] Funding Source: Medline
Osteoblasts are essential for maintaining bone mass, avoiding osteoporosis, and repairing injured bone. Activation of osteoblast G protein-coupled receptors (GPCRs), such as the parathyroid hormone receptor, can increase bone mass; however, the anabolic mechanisms are poorly understood. Here we use Rs1, an engineered GPCR with constitutive G(s) signaling, to evaluate the temporal and skeletal effects of G(s) signaling in murine osteoblasts. In vivo, Rs1 expression induces a dramatic anabolic skeletal response, with midfemur girth increasing 1,200% and femur mass increasing 380% in 9-week-old mice. Bone volume, cellularity, areal bone mineral density, osteoblast gene markers, and serum bone turnover markers were also elevated. No such phenotype developed when Rs1 was expressed after the first 4 weeks of postnatal life, indicating an exquisite temporal sensitivity of osteoblasts to Rs1 expression. This pathway may represent an important determinant of bone mass and may open future avenues for enhancing bone repair and treating metabolic bone diseases.
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