Advanced glycation end products induce cell cycle arrest and proinflammatory changes in osteoarthritic fibroblast-like synovial cells

• DOI: 10.1186/ar2807
• Publication Date: 2009-09-08T06:15:19Z
• Authors: Sybille Franke; Manfred Sommer; Christiane Rüster; Tzvetanka Bondeva; Julia Marticke; Gunther Hofmann; Gert Hein; Gunter Wolf
• Keywords: Proinflammatory cytokine

Advanced glycation end products (AGEs) have been introduced to be involved in the pathogenesis of osteoarthritis (OA). The influence AGEs on osteoarthritic fibroblast-like synovial cells (FLS) has incompletely understood as yet. present study investigates a potential AGE-modified bovine serum albumin (AGE-BSA) cell growth, and expression proinflammatory osteoclastogenic markers cultured FLS.FLS were established from OA joints stimulated with AGE-BSA. mRNA p27Kip1, RAGE (receptor for AGEs), nuclear factor kappa B subunit p65 (NFkappaB p65), tumor necrosis alpha (TNF-alpha, interleukin-6 (IL-6), receptor activator NFkappaB ligand (RANKL) osteoprotegerin was measured by real-time PCR. respective protein evaluated western blot analysis or ELISA. activation investigated luciferase assay electrophoretic mobility shift (EMSA). Cell cycle analysis, proliferation early apoptosis assessed. specificity response tested presence an anti-RAGE antibody.AGE-BSA actively taken up into determined immunohistochemistry blots. AGE-induced p27Kip1 associated arrest increase necrotic, but not apoptotic cells. confirmed EMSAs including supershift experiments. Anti-RAGE antibodies attenuated all AGE-BSA induced responses. increased RAGE, IL-6 TNF-alpha together indicates AGE-mediated inflammation. decreased RANKL may reflect diminished potential.The demonstrates that modulate growth genes pathophysiological process OA. This lead functional structural impairment joints.