High glucose stimulates adipogenic and inhibits osteogenic differentiation in MG-63 cells through cAMP/protein kinase A/extracellular signal-regulated kinase pathway.
Patients with diabetes tend to have an increased incidence of osteoporosis that may be related to hyperglycemia. In this study, we investigated the effects of high glucose on differentiation of human osteoblastic MG-63 cells and involved intracellular signal transduction pathways. Here, we showed that high glucose suppressed the cell growth, mineralization, and expression of osteogenic markers including Runx2, collagen I, osteocalcin, osteonectin, but inversely promoted expression of adipogenic markers including PPARgamma, aP2, resistin, and adipsin. Moreover, high glucose significantly increased the intracellular cAMP level in a time-dependent manner and induced ERK1/2 activation. Meanwhile, supplementation of H89, a specific inhibitor of PKA, and PD98059, a specific inhibitor of MAPK/ERK kinase, reversed the cell growth inhibition, the down-regulation of osteogenic markers and the up-regulation of adipogenic markers as well as the activation of ERK under high glucose. These results indicate that high glucose can increase adipogenic and inhibit osteogenic differentiation by activating cAMP/PKA/ERK pathway in MG-63 cells, thereby providing further insight into the molecular mechanism of diabetic osteoporosis.
Wang
Weiwei
W
College of Life Science, Graduate University of Chinese Academy of Sciences, Beijing, People's Republic of China.
Zhang
Xiaolin
X
Zheng
Jiaqiang
J
Yang
Jianhong
J
D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002113:Calcification, Physiologic / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D024042:Collagen Type I / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D048909:Diabetes Complications / Q000503:physiopathology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D010024:Osteoporosis / Q000209:etiology / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects*
D015415:Biomarkers; D024042:Collagen Type I; D004791:Enzyme Inhibitors; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; D005947:Glucose