Effects of Advanced Glycation End Products on Differentiation and Function of Osteoblasts and Osteoclasts

• Published in: Journal of Korean medical science 2021, 36(37), , pp.1-11
• Main Authors: Park, So Young, Choi, Kyoung Hee, Jun, Ji Eun, Chung, Ho Yeon
• Format: Article
• Language: English
• Subjects: Animals; Bone Marrow Cells - cytology; Cell Differentiation - drug effects; Cell Line; Glucose - pharmacology; Glycation End Products, Advanced - pharmacology; Intercellular Adhesion Molecule-1 - genetics; Intercellular Adhesion Molecule-1 - metabolism; JNK Mitogen-Activated Protein Kinases - genetics; JNK Mitogen-Activated Protein Kinases - metabolism; Macrophages - cytology; Macrophages - drug effects; Macrophages - metabolism; Male; Mice; Mice, Inbred ICR; Original; Osteoblasts - cytology; Osteoblasts - metabolism; Osteoclasts - cytology; Osteoclasts - metabolism; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; RANK Ligand - pharmacology; Receptor for Advanced Glycation End Products - genetics; Receptor for Advanced Glycation End Products - metabolism; 의학일반
• ISSN: 1011-8934; 1598-6357
• DOI: 10.3346/JKMS.2021.36.E239

Risk of fragility fractures increases in patients with diabetes mellitus, independent of bone mineral density. In the present study, the effects of advanced glycation end products (AGEs) on differentiation and function of osteoblasts and osteoclasts were investigated. AGEs and 25 mM glucose were administered to marrow-derived macrophages and MCT3T3-E1 cells. The effects of AGEs on osteoclast differentiation was investigated using tartrate-resistant acid phosphatase (TRAP) assay. The effects of AGEs on osteoblast differentiation was investigated using alkaline phosphatase (ALP) activity and bone nodule formation assays. Expression of osteoclast-specific and osteoblast-specific genes and effects on cell signaling pathways associated with cell differentiation were analyzed using reverse transcription polymerase chain reaction and western blotting. AGEs significantly decreased TRAP-positive multinucleated cell formation in receptor activator of nuclear factor-κB ligand-induced marrow-derived macrophages in a dose-dependent manner. AGEs suppressed the expression of osteoclast-specific genes, JNK, p38, AKT, intercellular adhesion molecule 1, and lymphocyte function-associated antigen 1 in marrow-derived macrophages. AGEs decreased ALP activity and showed a tendency to decrease bone nodule formation in MC3T3-E1 cells. AGEs suppressed the expression of osteoblast-specific genes, lysyl hydroxylase and lysyl oxidase in MC3T3-E1 cells. AGEs suppressed differentiation and function of osteoclasts and osteoblasts, and collagen cross-linking activity. It suggests that AGE may induce bone fragility through low bone turnover and deterioration of bone quality.