title: Autophagy impairment aggravates the inhibitory effects of high glucose on osteoblast viability and function.
abstract: Autophagy is a highly regulated homoeostatic process involved in the lysosomal degradation of damaged cell organelles and proteins. This process is considered an important pro-survival mechanism under diverse stress conditions. A diabetic milieu is known to hamper osteoblast viability and function. In the present study, we explored the putative protective role of autophagy in osteoblastic cells exposed to an HG (high glucose) medium. HG was found to increase protein oxidation and triggered autophagy by a mechanism dependent on reactive oxygen species overproduction in osteoblastic MC3T3-E1 cells. MC3T3-E1 cell survival was impaired by HG and worsened by chemical or genetic inhibition of autophagy. These findings were mimicked by H2O2-induced oxidative stress in these cells. Autophagy impairment led to both defective mitochondrial morphology and decreased bioenergetic machinery and inhibited further osteoblast differentiation in MC3T3-E1 cells upon exposure to HG. These novel findings indicate that autophagy is an essential mechanism to maintain osteoblast viability and function in an HG environment.
authors: §Instituto de Investigación Sanitaria (IIS)-Fundación Jiménez Díaz, Avda. Reyes Católicos, 2. 28040 Madrid, Spain.
authors: Alberto
authors: A
authors: Bartolomé
authors: Ana
authors: A
authors: López-Herradón
authors: Sergio
authors: S
authors: Portal-Núñez
authors: Ana
authors: A
authors: García-Aguilar
authors: Pedro
authors: P
authors: Esbrit
authors: Manuel
authors: M
authors: Benito
authors: Carlos
authors: C
authors: Guillén
mesh_terms: D000818:Animals; D001343:Autophagy; D002454:Cell Differentiation; D002460:Cell Line; D002470:Cell Survival; D005947:Glucose / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology
chemical_list: D006861:Hydrogen Peroxide; D005947:Glucose