Mechanism of Osteoclast Differentiation Regulated by Akt-Gsk3β-Nfatc1 Signal Pathway Mediated by Gαi1/3 Protein
Shi Ce
Gao Yun
Yang Guanghui
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,Gαi1/3-shRNA 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.
Keywords：Gαi1/3 proteinmacrophage colony stimulating factorbone marrow-derived macrophagesosteoporosis
Publication Date：2023-12-25
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：5( 1095-1099 )