Advanced glycation end products inhibit the osteogenic differentiation potential of adipose‐derived stem cells in mice through autophagy

Abstract: Diabetes microenvironment will accelerate the accumulation of Advanced glycation end products (AGEs), therefore, AGEs are a signature product in the study of the diabetes microenvironment. Adipose-derived stem cells (ASCs) have poor osteogenesis in the diabetes microenvironment, but the mechanism of the altered osteogenic potential of ASCs has not been elucidated. Bone tissue engineering by ASCs is widely used in the treatment of bone defects with diabetic osteoporosis. Therefore, this study investigated the effects of AGEs on osteogenic differentiation potential of ASCs and the underlying mechanisms. In the present study, we isolated and cultured ASCs in C57BL/6 mice, then treated ASCs with AGEs, the levels of autophagy and osteogenesis-related factors were decreased in the AGE-treated group. In order to verify autophagy and AGE-mediated changes in the osteogenic capacity of ASCs, we used 3-methyladenine, and rapamycin. After cotreatment with 3-methyladenine and AGEs, the levels of osteogenesis and autophagy were reduced more significantly, whereas rapamycin ameliorated the autophagy level and osteogenic differentiation potential of ASCs treated with AGEs. This study shows that AGEs can reduce the osteogenic differentiation potential of ASCs through autophagy, which may provide a reference for the treatment of bone defects with diabetes osteoporosis.