Continuous mild stimulation with advanced glycation end products reduce aggrecan and type II collagen production via the RAGE without inducing cell death in human OUMS-27 chondrosarcoma cells

Chondrocytes are responsible for the production of extracellular matrix (ECM) components of cartilage, such as collagen type II alpha-1 (COL2A1) and aggrecan, which are loosely distributed in articular cartilage. Chondrocyte dysfunction has been implicated in the pathogenesis of rheumatic diseases, such as osteoarthritis (OA) and rheumatoid arthritis (RA). Advanced glycation end products (AGEs) accumulate in all tissues and body fluids, including cartilage and synovial fluid, with aging. Their accumulation in vivo is one of the major factors that cause and accelerate pathological changes in some chronic diseases, such as OA. Glycolaldehyde-derived AGEs (AGE3), known as toxic AGEs, have the strongest effect on cartilage compared to other AGEs. Studies conducted to date to demonstrate the effects of AGEs on chondrocytes have used very high doses (100 µg/mL) and collagen and aggrecan were reduced in the short term (24 h) due to decreased chondrocyte cell viability. However, it is assumed that AGEs stimulate cells for a longer period of time in vivo without causing cell death. Therefore, we stimulated a human chondrosarcoma cell line (OUMS-27) with 10 µg/mL AGE3 for four weeks. As a result, the expression of COL2A1 and aggrecan was significantly downregulated in OUMS-27 cells without inducing cell death, but the expression of proteases that play an important role in cartilage destruction was not affected. In addition, the receptor for advanced glycation end products (RAGE) inhibitors suppressed the AGE3-induced reduction in cartilage component production, suggesting the involvement of RAGE in the action of AGE3.