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Exercise increases bone mass by lactate/Gpr81 signaling pathway.

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Area of Science:

  • Bone biology and exercise physiology

Background:

  • Exercise is crucial for bone health, but its precise mechanisms remain unclear.
  • High-intensity interval training (HIIT) shows promise for improving bone mineral density (BMD).

Purpose of the Study:

  • To investigate the role of lactate, a HIIT byproduct, in regulating bone homeostasis.
  • To elucidate the molecular pathways involved in lactate-mediated bone remodeling.
  • To evaluate the efficacy of HIIT and lactate administration in an osteoporosis mouse model.

Main Methods:

  • In vitro studies using osteoblasts and osteoclasts, including Gpr81-deficient cells.
  • Analysis of signaling pathways (Gpr81-TAK1-p65 and Gpr81-Wnt/β-catenin).
  • In vivo studies using ovariectomized (OVX) mice subjected to HIIT or lactate treatment.

Main Results:

  • Lactate promotes osteoblast differentiation and inhibits osteoclast differentiation, mediated by Gpr81.
  • Lactate activates distinct signaling pathways for osteoblast and osteoclast regulation.
  • HIIT and direct lactate administration attenuated bone loss and improved bone mass in OVX mice.

Conclusions:

  • Lactate plays a key role in exercise-induced bone homeostasis via Gpr81 signaling.
  • Targeting the Gpr81 pathway presents a potential therapeutic strategy for osteoporosis prevention and treatment.