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TDAG8 activation inhibits osteoclastic bone resorption

Hisako Hikiji1, Daisuke Endo, Kyoji Horie

  • 12Department of Immunology, Graduate School of Medicine, Akita University, 1-1-1 Hondo, Akita City, Akita 010-8543, Japan. satishii@med.akita-u.ac.jp.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|November 14, 2013
PubMed

Insights

Proton-sensing receptor TDAG8 influences bone resorption. TDAG8 gene mutation exacerbated bone loss, suggesting TDAG8 enhancement may prevent osteoporosis.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Physiology

Background:

  • The role of acids in bone metabolism is known, but proton-sensing receptors' functions are unexplored.
  • Osteoporosis is a bone disease characterized by bone loss and increased fracture risk.

Purpose of the Study:

  • To investigate the role of proton-sensing receptor T-cell death-associated gene 8 (TDAG8) in osteoclastic activity and bone metabolism.
  • To explore TDAG8's function in bone loss following ovariectomy.

Main Methods:

  • Ovariectomy was performed on mice with Tdag8 gene mutations.
  • Bone mineral content was measured.
  • Osteoclast activity and calcium resorption were assessed in vitro.
  • Osteoclast formation under acidic conditions was evaluated using bone marrow cell cultures.
  • The TDAG8-Rho signaling pathway was investigated.

Main Results:

  • Pathological bone resorption was significantly exacerbated in mice homozygous for the Tdag8 gene mutation.
  • Osteoclasts from homozygous mutant mice showed increased calcium resorption in vitro.
  • Tdag8 gene mutation ameliorated impaired osteoclast formation under acidic conditions.
  • Extracellular acidification altered osteoclast cell morphology through the TDAG8-Rho signaling pathway.

Conclusions:

  • TDAG8 plays a crucial role in regulating osteoclastic activity and bone metabolism.
  • Enhancing TDAG8 function presents a potential therapeutic strategy for preventing bone resorption diseases like osteoporosis.
Keywords:
GPR65RhoT-cell death-associated gene 8cell morphologyproton-sensing receptor

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