title: Advanced glycation end products biphasically modulate bone resorption in osteoclast-like cells.
abstract: Advanced glycation end products (AGEs) disturb bone remodeling during aging, and this process is accelerated in diabetes. However, their role in modulation of osteoclast-induced bone resorption is controversial, with some studies indicating that AGEs enhance bone resorption and others showing the opposite effect. We determined whether AGEs present at different stages of osteoclast differentiation affect bone resorption differently. Based on increased levels of tartrate-resistant acid phosphatase (TRAP) and cathepsin K (CTSK), we identified day 4 of induction as the dividing time of cell fusion stage and mature stage in RAW264.7 cell-derived osteoclast-like cells (OCLs). AGE-modified BSA (50-400 μg/ml) or control BSA (100 μg/ml) was then added at the beginning of each stage. Results showed that the presence of AGEs at the cell fusion stage reduced pit numbers, resorption area, and CTSK expression. Moreover, expression of receptor activator of nuclear factor-κB (RANK) as well as the number of TRAP-positive cells, nuclei per OCL, actin rings, and podosomes also decreased. However, the presence of AGEs at the mature stage enlarged the resorption area markedly and increased pit numbers slightly. Intriguingly, only the number of nuclei per OCL and podosomes increased. These data indicate that AGEs biphasically modulate bone resorption activity of OCLs in a differentiation stage-dependent manner. AGEs at the cell fusion stage reduce bone resorption dramatically, mainly via suppression of RANK expression in osteoclast precursors, whereas AGEs at the mature stage enhance bone resorption slightly, most likely by increasing the number of podosomes in mature OCLs.
authors.affiliation: Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; and.
authors.forename: Ziqing
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Chaohong
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yuhuan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; and.
authors.forename: Weishen
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; and.
authors.forename: Guotian
authors.initials: G
authors.lastname: Luo
authors.affiliation: Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; and.
authors.forename: Ziji
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; and.
authors.forename: Haixing
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; and.
authors.forename: Yangchun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; and.
authors.forename: Dongliang
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; and shengpuyi@hotmail.com.
authors.forename: Puyi
authors.initials: P
authors.lastname: Sheng
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000199:Actins / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D016723:Bone Remodeling / Q000187:drug effects*; D001862:Bone Resorption / Q000378:metabolism*; D056657:Cathepsin K / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000069261:Podosomes / Q000187:drug effects / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000187:drug effects / Q000378:metabolism; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D000199:Actins; D017127:Glycation End Products, Advanced; D007527:Isoenzymes; D053246:Receptor Activator of Nuclear Factor-kappa B; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase; D056657:Cathepsin K; C534132:Ctsk protein, mouse
keywords: advanced glycation end products; bone resorption; osteoclast; podosome; receptor activator of nuclear factor-κB