| G protein-coupled receptor 48 (GPR48), a leucine-rich membrane-spanning seven-transmembrane receptor whose LRR domain binds to R-spondin1 or Norrin to form a complex, can act on downstream key factors that regulate osteoporosis, Alzheimer's disease, high blood pressure and other diseases. Bone, as an important physiological and biomechanical tissue, is balanced between bone formation and bone resorption dominated by osteoblasts (OB) and osteoclasts (OC) synergistically. Osteocytes, which are mechanically stimulated and sensitive cells, regulate the bone-adaptive response after stress loading. The mechanical stimulation of the bone during exercise training translates into structural cascade biochemical reactions (Wnt, cAMP/PKA/Atf4, OPG/RANKL/RANK and other means of steady-state expression), regulating bone formation and/or bone resorption. Moreover, GPR48 directly regulates the activation of the above signaling pathways via R-spondin1. Does GPR48 through the downstream cascade signaling pathways in the exercise of bone metabolism play a role in molecular mediation? Exploration the role of GPR48 in bone metabolism and its molecular mechanisms of exercise may improve the understanding of the signaling networks in bone metabolism and provide a new target for the diagnosis and treatment of bone diseases and non-drug interventions. |