Osteoking ameliorates type 2 diabetes osteoporosis by promoting osteoblasts proliferation via PI3K/AKT/GSK-3β pathway activation

Abstract

Abstract Osteoking (OK) is a Yi folk Chinese herb from the Yunnan province, which exerts bone formation-promoting effects on menopausal osteoporosis and osteoporotic fractures. However, it remains to be determined whether OK ameliorates type 2 diabetic osteoporosis (T2DOP). Thus, T2DOP animal model was established in db/db mice in this study. Micro-computed tomography (micro-CT) analysis revealed that OK significantly increased bone strength, improved bone metabolism, and promoted bone formation. GS and p-GSK-3β expression levels were increased in OK group as compared with db/db group by Western blot analysis. IL-6, IL-17A, IFN-γ, TNF-α, and IL-1β were lower levels in the OK group compared to the db/db group, nevertheless, the IL-10 level was significantly higher. Furthermore, an In vitro cells model was constructed by stimulating with high glucose (HG, 30 mM). ALP protein was significantly elevated in OK treatment group. Administration of OK at 1.44 mg/mL significantly increased p-AKT/AKT expression, while, combined with LY294002, an inhibitor of PI3K, OK significantly reduced the expression levels of p-PI3K/PI3K, p-AKT/AKT and p-GSK-3β/GSK-3β. In conclusion, to our knowledge, this study is the first to reveal OK exhibits efficacy against T2DOP in db/db mice by promoting osteogenesis of preosteoblast MC3T3-E1 cells through PI3K/AKT/GSK-3β pathway regulation.