The result observed that the ratio of OPG/RANKL in T2DM was 0.81 and that this value rose to a height of 1.25 after GLP-1 treatment. GLP-1RA of Exendin-4 mainly inhibited bone resorption by regulating OPG/RANKL ratio, and increases the expression of osteogenic related genes OC, COL1, Runx2, and ALP to promote bone formation (Ma et al., 2013). In addition, this study detected OPG and RANKL mRNA expression and serum concentration. The OPG/RANKL signaling system is critical in the pathogenesis of bone related diseases caused by increased bone resorption (Hofbauer and Schoppet, 2004; Yang et al., 2020). Nuche-Berenguer et al. Previous research in our team found that GLP-1RA (geniposide) could significantly increase the mRNA and protein expression of OPN, Runx2, and Osterix in DEX-treated MC3T3-E1 cells by activating the ERK MAPK signaling pathway. The PI3K/AKT signaling pathway plays an important role in regulating proliferation, osteoblast differentiation and osteoclast differentiation, apoptosis (Zhang et al., 2020; Ye et al., 2019). Studies have shown that GLP-1RA can regulate PI3K/AKT signaling pathway through GLP-1R to alleviate cell apoptosis (Xie et al., 2018; Ming-Yan et al., 2019). In addition, liraglutide could increase intracellular cAMP level and phosphorylation of AKT and the inhibitors LY294002, and GLP-1R siRNA could partially block the liraglutide-induced signaling activation and attenuated the facilitating effect of liraglutide.

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