Advanced Glycation End Products Affect Osteoblast Proliferation and Function by Modulating Autophagy Via the RAGE/Raf/MEK/ERK Pathway. [Molecular Bases of Disease]
October 15th, 2015 by Meng, H.-Z., Zhang, W.-L., Liu, F., Yang, M.-W.
The interaction between advanced glycation end products (AGEs) and receptor of AGEs (RAGE) is associated with the development and progression of diabetes-associated osteoporosis, but the mechanisms involved are still poorly understood. In this study, we found that AGE-modified bovine serum albumin (AGE-BSA) induced a biphasic effect on the viability of hFOB1.19 cells: cell proliferation was stimulated after exposure to low-dose AGE-BSA, but cell apoptosis was stimulated after exposure to high-dose AGE-BSA. The low-dose AGE-BSA facilitates proliferation of hFOB1.19 cells by concomitantly promoting autophagy, RAGE production, and the Raf / MEK / ERK signaling pathway activation. Furthermore, we investigated the effects of AGE-BSA on the function of hFOB1.19 cells. Interestingly, the results suggest that the short-term effects of low-dose AGE-BSA increase osteogenic function and decrease osteoclastogenic function, which are likely mediated by autophagy and the RAGE/Raf/MEK/ERK signal pathway. In contrast, with increased treatment time, the opposite effects were observed. Collectively, AGE-BSA had a biphasic effect on the viability of hFOB1.19 cells in vitro, which was determined by the concentration of AGE-BSA and treatment time. A low concentration of AGE-BSA activated the Raf/MEK/ERK signal pathway through the interaction with RAGE, induced autophagy and regulated the proliferation and function of hFOB1.19 cells.