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Like normal healthy disc tissues, articular cartilage in synovial joints is avascular. Osteoarthritis (OA) is the most common form of arthritis that is characterized by loss of joint form and function due to progressive articular cartilage degeneration. Articular cartilage is mostly composed of water and ECM proteins, with a sparsely distributed population of highly specialized chondrocytes Alizarin embedded within a matrix that make up http://www.selleckchem.com/products/SB-203580.html osteophytes at the joint margins, and bony sclerosis or increased density or thickness of the bone just underneath the articular cartilage. Other aging-related changes in articular cartilage include fibrillation of the articular surface, decrease in the size and aggregation of aggrecans and increased collagen cross-linking.20 These lead to the loss of tensile strength and joint stiffness. Aggrecan complexes shrink with age and are structurally altered due to proteolytic modification of the core protein as well as changes in the length and abundance of glycosaminoglycan side-chains.21 These changes are most likely selleck products the consequence of altered chondrocyte function. Aged chondrocytes characteristically have decreased ECM protein synthesis and reduced responsiveness to anabolic growth factors; they also produce less link proteins, smaller and less uniform aggrecan.20, 21 Recent work suggests that there is progressive senescence of articular cartilage chondrocytes, as evident by increased expression of the cell senescence markers P16/INK4A and senescence-associated beta-galactosidase (SA-beta-gal) and decreased telomere length with age.22, 23 Aging is caused at least in part by the time-dependent accumulation of cellular and molecular damage leading to a progressive decline in functional reserve.8, 24 Traditionally it was assumed that continuous mechanical wear and tear is the primary basis of joint damage. However, there is growing evidence for oxidative damage, a known driver of cell senescence, in aged disc and articular cartilage, as a principal driving force of joint degeneration.25, 26 Immunomorphological analysis revealed a higher level of carboxymethyl-lysine (CML; a biomarker of oxidized protein) in degenerated IVDs from aged patients compared to young normal discs.27 Similarly, NF-��B, a transcription factor activated in response to cellular stress, including oxidative stress, is increased in old discs.