Regulation of bone formation and remodeling by G-protein-coupled receptor 48

Jian Luo, Wei Zhou, Xin Zhou, Dali Li, Jinsheng Weng, Zhengfang Yi, Sung Gook Cho, Chenghai Li, Tingfang Yi, Xiushan Wu, Xiao Ying Li, Benoit de Crombrugghe, Magnus Höök, Mingyao Liu

Research output: Contribution to journalArticle

117 Scopus citations

Abstract

G-protein-coupled receptor (GPCR) 48 (Gpr48; Lgr4), a newly discovered member of the glycoprotein hormone receptor subfamily of GPCRs, is an orphan GPCR of unknown function. Using a knockout mouse model, we have characterized the essential roles of Gpr48 in bone formation and remodeling. Deletion of Gpr48 in mice results in a dramatic delay in osteoblast differentiation and mineralization, but not in chondrocyte proliferation and maturation, during embryonic bone formation. Postnatal bone remodeling is also significantly affected in Gpr48-/- mice, including the kinetic indices of bone formation rate, bone mineral density and osteoid formation, whereas the activity and number of osteoclasts are increased as assessed by tartrate-resistant acid phosphatase staining. Examination of the molecular mechanism of Gpr48 action in bone formation revealed that Gpr48 can activate the cAMP-PKA-CREB signaling pathway to regulate the expression level of Atf4 in osteoblasts. Furthermore, we show that Gpr48 significantly downregulates the expression levels of Atf4 target genes/proteins, such as osteocalcin (Ocn; Bglap2), bone sialoprotein (Bsp; Ibsp) and collagen. Together, our data demonstrate that Gpr48 regulates bone formation and remodeling through the cAMP-PKA-Atf4 signaling pathway.

Original languageEnglish (US)
Pages (from-to)2747-2756
Number of pages10
JournalDevelopment
Volume136
Issue number16
DOIs
StatePublished - Aug 15 2009

Keywords

  • Atf4
  • Bone formation
  • Bone remodeling
  • Gpr48 (Lgr4)
  • Mouse

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology

Fingerprint Dive into the research topics of 'Regulation of bone formation and remodeling by G-protein-coupled receptor 48'. Together they form a unique fingerprint.

Cite this