Diabetes, Metabolic Syndrome and Obesity (Mar 2020)
Catalpol Promotes the Proliferation and Differentiation of Osteoblasts Induced by High Glucose by Inhibiting KDM7A
Abstract
Jian Cheng,1,2,* Hai-yan Xu,3,* Ming-ming Liu,4 Jian-ping Cai,2 Lei Wang,2 Zhen Hua,2 Xiao-dong Wu,1 Wei-ling Huo,1 Nan-ning Lv4 1Department of Orthopedics, Xuzhou Central Hospital Affiliated to Nanjing University of Chinese Medicine, Xuzhou, Jiangsu 221009, People’s Republic of China; 2Institute of Traumatology & Orthopedics, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, People’s Republic of China; 3Department of Human Anatomy, Xuzhou Medical University, Xuzhou, Jiangsu 221004, People’s Republic of China; 4Department of Orthopedic Surgery, Lianyungang Second People’s Hospital, Lianyungang 222023, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ming-ming LiuDepartment of Orthopedic Surgery, Lianyungang Second People’s Hospital, No. 41 Hailian East Road, Haizhou District, Lianyungang, Jiangsu 222023, People’s Republic of ChinaEmail [email protected] CaiInstitute of Traumatology & Orthopedics, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, People’s Republic of ChinaEmail [email protected]: 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: catalpol, KDM7A, proliferation, differentiation, osteoblasts, high glucose
