AUTHOR=Xie Baocheng , Zeng Zhanwei , Liao Shiyi , Zhou Chenhui , Wu Longhuo , Xu Daohua TITLE=Kaempferol Ameliorates the Inhibitory Activity of Dexamethasone in the Osteogenesis of MC3T3-E1 Cells by JNK and p38-MAPK Pathways JOURNAL=Frontiers in Pharmacology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.739326 DOI=10.3389/fphar.2021.739326 ISSN=1663-9812 ABSTRACT=

Kaempferol has been reported to exhibit beneficial effect on the osteogenic differentiation in mesenchymal stem cells (MSC) and osteoblasts. In our previous study, dexamethasone (DEX) demonstrated inhibitory effect on MC3T3-E1 cells differentiation. In this study, we mainly explored the protective effect of kaempferol on the inhibitory activity of DEX in the osteogenesis of MC3T3-E1 cells. We found that kaempferol ameliorated the proliferation inhibition, cell cycle arrest, and cell apoptosis and increased the activity of alkaline phosphatase (ALP) and the mineralization in DEX-treated MC3T3-E1 cells. Kaempferol also significantly enhanced the expression of osterix (Osx) and runt-related transcription factor 2 (Runx2) in MC3T3-E1 cells treated with DEX. In addition, kaempferol attenuated DEX-induced reduction of cyclin D1 and Bcl-2 expression and elevation of p53 and Bax expression. Kaempferol also activated JNK and p38-MAPK pathways in DEX-treated MC3T3-E1 cells. Furthermore, kaempferol improved bone mineralization in DEX-induced bone damage in a zebrafish larvae model. These data suggested that kaempferol ameliorated the inhibitory activity of DEX in the osteogenesis of MC3T3-E1 cells by activating JNK and p38-MAPK signaling pathways. Kaempferol exhibited great potentials in developing new drugs for treating glucocorticoid-induced osteoporosis.