High glucose inhibits osteogenic differentiation through the BMP signaling pathway in bone mesenchymal stem cells in mice.
Patients with diabetes tend to have an increased risk of osteoporosis that may be related to hyperglycemia. In vitro evidence has shown that high glucose can affect the proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs). Tissue regeneration depends mainly on MSCs. However, the exact mechanisms involved in high glucose-induced bone loss remain unknown. In this study, we investigated the effects of high glucose on the proliferation and osteogenic differentiation of mice bone MSCs (BMSCs) and determined the specific mechanism of bone morphogenetic protein 2 (BMP-2) in the osteogenic differentiation of mice BMSCs in a high-glucose microenvironment. High glucose (< 25 mM) promoted cell growth but suppressed mineralization. The intracellular BMP-2 level in BMSCs cultured in a high-glucose microenvironment was significantly decreased and suppressed activation of the BMP signaling pathway. Consequently, expression of the osteogenic markers Runx2, alkaline phosphatase, and osteocalcin were decreased. Meanwhile, supplementation with ectogenic BMP-2 reversed the cell osteogenic differentiation and osteogenic marker down-regulation under high glucose. Our data indicate that BMP-2 plays an important role in regulating the osteogenic differentiation of BMSCs in a high-glucose microenvironment. Thus, it is possible that agents modifying this pathway could be used by BMSCs to promote bone regeneration in high-glucose microenvironments.
Department of Stomatology, Chinese PLA General Hospital and Postgraduate Military Medical School, Beijing 100853, China.
Juncheng
J
Wang
Department of Stomatology, Chinese PLA The Military General Hospital of Beijing, Beijing 100700, China.
Bin
B
Wang
Department of Stomatology, Chinese PLA General Hospital and Postgraduate Military Medical School, Beijing 100853, China.
Ying
Y
Li
Department of Stomatology, Chinese PLA General Hospital and Postgraduate Military Medical School, Beijing 100853, China.
Dongsheng
D
Wang
Department of Stomatology, Chinese PLA General Hospital and Postgraduate Military Medical School, Beijing 100853, China.
E
E
Lingling
Department of Stomatology, Chinese PLA General Hospital and Postgraduate Military Medical School, Beijing 100853, China.
Yang
Y
Bai
Department of Stomatology, Chinese PLA General Hospital and Postgraduate Military Medical School, Beijing 100853, China.
Hongchen
H
Liu
BMP-2; bone mesenchymal stem cells; high glucose; molecular pathways; osteogenic differentiation