TDAG8 activation inhibits osteoclastic bone resorption.

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.