Icariin regulates the osteoblast differentiation and cell proliferation of MC3T3-E1 cells through microRNA-153 by targeting Runt-related transcription factor 2

Exp Ther Med. 2018 Jun;15(6):5159-5166. doi: 10.3892/etm.2018.6127. Epub 2018 May 3.

Abstract

Osteoporosis has become one of the most serious public health problems. Icariin, miR-153 and Runt-related transcription factor 2 (Runx2) have been demonstrated to regulate cell proliferation and differentiation in multiple cells. The aim of the present experiments was to investigate the potential mechanism underlying osteoblast differentiation and cell proliferation of MC3T3-E1 cells treated with icariin. Cell Counting kit-8, alkaline phosphatase (ALP) activity and alizarin red S assays, as well as reverse transcription-quantitative polymerase chain reaction and western blot analysis, were performed to examine whether icariin promoted osteoblast differentiation and cell proliferation in MC3T3-E1 cells. Subsequently, miR-153 target and pathway prediction, and functional analysis were assessed. The results demonstrated that icariin promoted proliferation, mineral content and ALP activity in MC3T3-E1 cells. In addition, miR-153 and Runx2 expression levels were increased following treatment with icariin. Luciferase assay revealed that miR-153 significantly upregulate the luciferase activity of wild-type (Wt) Runx2 3'-untranslated region. Furthermore, the group treated with a combination of miR-153 mimics and icariin exhibited a significantly higher expression of Runx2 in comparison with the miR-153 mimic-treated alone group. Finally, icariin reversed the potential effect of miR-153 inhibitor in MC3T3-E1 cells. In conclusion, icariin exerted a strong osteoblast differentiation effect in MC3T3-E1 cells through the miR-153/Runx2 pathway. The current study provided evidence suggesting that icariin should be considered as an effective candidate for the management of osteoporosis.

Keywords: Runt-related transcription factor 2; icariin; microRNA-153; osteoblast differentiation; osteoporosis.