Catalpol Promotes the Proliferation and Differentiation of Osteoblasts Induced by High Glucose by Inhibiting KDM7A

Diabetes Metab Syndr Obes. 2020 Mar 13:13:705-712. doi: 10.2147/DMSO.S246433. eCollection 2020.

Abstract

Introduction: The protective effect of catalpol on diabetic osteoporosis (DOP) and its mechanism remain unclear. This study aimed to explore whether catalpol enhanced the proliferation and differentiation of MC3T3 cells induced by high glucose by inhibiting the expression of KDM7A.

Methods: MC3T3 cells were induced by high glucose (HG) and treated with different concentrations of catalpol. The proliferation and mineralization abilities of MC3T3-E1 cells were determined by CCK-8 assay and Alizarin Red Staining, respectively. The expression of differentiation-related osteogenic proteins, KDM7A and related proteins of Wnt/β-catenin signaling pathway was analyzed by Western blot analysis. The alkaline phosphatase (ALP) activity was detected by ALP assay kits.

Results: MC3T3-E1 cells induced by high glucose showed decreased proliferation and mineralization abilities and decreased ALP activity, which were all reversed by the treatment of catalpol. High glucose induction inhibited the expression of KDM7A, Total-β-catenin, Nuclear-β-catenin and p-GSK3β, which was reversed by the treatment of catalpol. And KDM7A interference up-regulated the expression of Total-β-catenin, Nuclear-β-catenin and p-GSK3β, which was down-regulated by KDM7A overexpression. Furthermore, the proliferation and mineralization abilities and ALP activity were improved when treated with KDM7A interference and decreased when treated with KDM7A overexpression. However, SKL2001 could improve the proliferation and mineralization abilities and ALP activity of MC3T3-E1 cells.

Discussion: Catalpol promotes the proliferation and differentiation of osteoblasts induced by high glucose by regulating the Wnt/β-catenin signaling pathway through KDM7A.

Keywords: KDM7A; catalpol; differentiation; high glucose; osteoblasts; proliferation.

Grants and funding

Natural Science Foundation of Jiangsu Province (BK20180996); Project of Jiangsu Bureau of traditional Chinese Medicine (YB201964) and the 16th batch of “Six Talent Peak” project of Jiangsu Province (WSN-282).