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Abstract Objective To investigate the regulation of Gαi1/3 protein on osteoclast differentiation of bone marrow-derived macrophages (BMMs)and its mechanism. Methods Three BMMs，scr-shRNA，Gαi1/3-shRNA and Gαi1/3-DKO，were obtained by lentivirus knockdown and gene knockout strategies，and were treated with macrophage colony stimulating factor(MCSF)，receptor activator for nuclear factor-κB ligand (RANKL)and MCSF+RANKL for 30min.Western Blot was used to detect the expression of key proteins in the Akt-GSK3β-NFATc1 signaling pathway.MCSF and RANKL were combined to induce scr-shRNA，Gαi1/3shRNA BMMs 4 days.TRAP staining were used to observe the number of cell nuclei and the size and number of osteoclasts.Lentivirus scr-shRNA and Gαi1/3 shRNA were injected into the right epiphysis of the femoral shaft of a mouse model of osteoporosis to observe the reverse effect of Gαi1/3 knockdown on bone loss in mice.Results The activation of key proteins (p-Akt473，p-GSK3β，NFATc1)in the Akt-GSK3β-NFATc1 pathway induced by MCSF and MCSF+RANKL was inhibited by Gαi1/3.Knockdown of Gαi1/3 inhibits osteoclast differentiation and bone loss in mice in osteoporosis models.Conclusion Gαi1/3 protein regulates osteoclast differentiation by mediating Akt-GSK3β-NFATc1 pathway，which may provide a new idea and therapeutic target for the clinical treatment of osteoporosis.
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Corresponding Authors:
Yang Guanghui
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