Advanced glycation end products promote osteoporosis by inducing ferroptosis in osteoblasts
Abstract
Advanced glycation end products (AGEs) have been widely reported to play an important role in osteoporosis (OP), particularly in diabetes-related OP. The aim of the present study was to investigate the effect of AGEs on osteoblast function and the underlying mechanisms. The level of bone mineral density (BMD), serum AGEs and fasting blood glucose (FBG) was measured in patients with OP and healthy individuals, and the correlation between AGE levels and BMD or FBG was then analyzed. For the in vitro experiments, the hFOB1.19 osteoblast cell line was cultured in medium containing AGEs and serum from healthy individuals or patients with OP, and with or without type-2 diabetes mellitus (T2DM). Cell proliferation, differentiation, mineralization, apoptosis and ferroptosis were evaluated using Cell Counting Kit-8 and alkaline phosphatase (ALP) assays, Alizarin red and TUNEL staining, iron indicator, lipid peroxidation tests and western blot analysis, respectively. In a separate set of experiments, the ferroptosis inhibitor, deferoxamine (DFO), was also added to the culture medium of cells treated with AGEs and serum from patients with OP and T2DM. The results demonstrated that patients with OP had a higher level of serum AGEs and FBG compared with that in healthy individuals. The level of serum AGEs in patients with OP was negatively correlated with BMD, but was positively correlated with FBG. In addition, AGEs and serum from patients with OP markedly inhibited hFOB1.19 cell…
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