Int J Med Sci 2020; 17(17):2663-2672. doi:10.7150/ijms.44231

Research Paper

Dexamethasone inhibits BMP7-induced osteogenic differentiation in rat dental follicle cells via the PI3K/AKT/GSK-3β/β-catenin pathway

Jing Tang1,2, Mao-Feng Qing3, Min Li1,2, Zhi Gao1✉

1. Department of Stomatology, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing 400010, P.R. China.
2. Chongqing Key Laboratory of Oral Disease and Biomedical Sciences, 426 North Songshi Road, Yubei District, Chongqing 401147, P.R. China.
3. State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, Sec. 3, Renminnan Road, 610041 Chengdu, Sichuan, P.R. China.

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Citation:
Tang J, Qing MF, Li M, Gao Z. Dexamethasone inhibits BMP7-induced osteogenic differentiation in rat dental follicle cells via the PI3K/AKT/GSK-3β/β-catenin pathway. Int J Med Sci 2020; 17(17):2663-2672. doi:10.7150/ijms.44231. Available from http://www.medsci.org/v17p2663.htm

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Abstract

Impacted third molars are commonly seen in teenagers and young adults and can cause considerable suffering. Preventing eruption of the third molars can reduce pain at the source. Our previous study has shown that dexamethasone (DEX) at a certain concentration can prevent the eruption of third molars without damaging alveolar bone in Sprague-Dawley (SD) rats, but the relevant molecular mechanisms need to be explored. This study aimed to explore the effects of high concentrations of DEX on osteogenic signaling pathways, including BMP/Smad and Wnt/β-catenin pathways, in rat dental follicle cells (rDFCs) and to elucidate the possible mechanisms. The results showed that BMP7 induced osteogenic differentiation by increasing the activity of ALP and the protein levels of OPN in rDFCs. DEX decreased endogenous BMP7 and phosphorylated Smad1/5/8 expression as well as BMP7-induced osteogenic differentiation. DEX also reduced the mRNA and protein levels of β-catenin by enhancing the expression of GSK-3β. In addition, regardless of DEX intervention, overexpression of BMP7 promoted the expression of β-catenin, while knockdown of BMP7 attenuated it. Further investigation revealed that overexpression of BMP7 attenuated the DEX-mediated inhibition of AKT and GSK-3β phosphorylation, but knockdown of BMP7 exerted the opposite effects. This study suggests that high concentrations of DEX may inhibit the expression of β-catenin via the PI3K/AKT/GSK-3β pathway in a manner mediated by BMP7. The findings further illustrate the possible molecular mechanisms by which DEX prevents tooth development.

Keywords: dental follicle cells, Dexamethasone, bone morphogenetic protein 7, PI3K/AKT/GSK-3β/β-catenin