title: Advanced Glycation End Products Affect Osteoblast Proliferation and Function by Modulating Autophagy Via the Receptor of Advanced Glycation End Products/Raf Protein/Mitogen-activated Protein Kinase/Extracellular Signal-regulated Kinase Kinase/Extracellular Signal-regulated Kinase (RAGE/Raf/MEK/ERK) Pathway.
abstract: 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.
authors.affiliation: Department of Orthopaedics, First Affiliated Hospital, China Medical University, Shenyang 110001, China.
authors.forename: Hong-Zheng
authors.initials: HZ
authors.lastname: Meng
authors.affiliation: Department of Orthopaedics, First Affiliated Hospital, China Medical University, Shenyang 110001, China.
authors.forename: Wei-Lin
authors.initials: WL
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, First Affiliated Hospital, China Medical University, Shenyang 110001, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics, First Affiliated Hospital, China Medical University, Shenyang 110001, China. Electronic address: maoweiyang@hotmail.com.
authors.forename: Mao-Wei
authors.initials: MW
authors.lastname: Yang
mesh_terms: D001343:Autophagy / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation / Q000502:physiology*; D017127:Glycation End Products, Advanced / Q000502:physiology*; D006801:Humans; D020935:MAP Kinase Signaling System; D010006:Osteoblasts / Q000166:cytology*; D000067759:Receptor for Advanced Glycation End Products / Q000502:physiology*; D048490:raf Kinases / Q000378:metabolism*
chemical_list: C000593871:AGER protein, human; D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D048490:raf Kinases
keywords: advanced glycation end products (AGEs); autophagy; cell proliferation; extracellular-signal-regulated kinase (ERK); osteoblast; receptor for advanced glycation end products (RAGE)