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To assess collagen degradation and its relationship to some of the key collagenolytic proteinases in the aggressive synovial membrane–like interface tissue around aseptically loosened hip replacement implants.The medical indication for the primary total hip replacement was osteoarthritis in all study patients. Samples from the study patients were compared with control synovial membranes obtained from trauma (hip fracture) patients. Proteoglycans were extracted with 4M guanidinium chloride. Denatured collagen in the remaining matrix was solubilized with α‐chymotrypsin. Nonsoluble matrix and supernatant fractions were acid hydrolyzed before measurement of hydroxyproline. The proportion of soluble (in vivo–degraded) collagen of the total sample collagen content was calculated. Proteinases were stained using the avidin–biotin–peroxidase complex method.Collagen in the interface membrane from the implants was highly degraded (mean ± SEM 20 ± 3%) compared with that in the control synovial membranes (12 ± 1%; P = 0.007). In controls, the degree of collagen degradation did not correlate with levels of matrix metalloproteinase 1 (MMP‐1), MMP‐13, or cathepsin K, although MMP‐1 approached statistical significance. In interface membranes, the correlations were r = 0.88 (P = 0.002), r = 0.92 (P = 0.001), and r = 0.98 (P < 0.0001) for MMP‐1, MMP‐13, and cathepsin K, respectively.In normal synovial membrane, collagen matrix remodeling may be mainly an intracellular process. In contrast, pathologic tissue destruction in the interface membrane from prosthetic hip joints is associated with a shift toward MMP‐13 and cathepsin K, which become activated and overcome their endogenous inhibitors (tissue inhibitors of metalloproteinases and cystatin C). The highly significant correlation between collagen degradation and cathepsin K indicates an extracellular role of this acidic endoproteinase, consistent with previous observations concerning the acidity of the interface membrane. [ABSTRACT FROM AUTHOR]

The major risk factor for osteoarthritis (OA) is aging, but the mechanisms underlying this risk are only partly understood. Age‐related accumulation of advanced glycation end products (AGEs) could be one of these mechanisms. We undertook this study to investigate the role of the receptor for AGEs (RAGE) in mediating the cellular effects of AGEs on chondrocytes and fibroblast‐like synoviocytes (FLS).AGE levels in human cartilage were determined by fluorescence, browning, and pentosidine levels. Chondrocyte activation by AGEs was assessed as the release of proteoglycans and the synthesis of matrix metalloproteinase 1 (MMP‐1) and type II collagen messenger RNA (mRNA). The activation of FLS by AGEs was measured by MMP‐1 production and invasion through matrix proteins.Patients with focal degeneration of cartilage showed increased AGE levels in their healthy cartilage compared with the levels in healthy cartilage from donors without cartilage degeneration (P < 0.01 for both fluorescence and browning; P not significant for pentosidine content). Stimulation of bovine chondrocytes with glycated albumin increased the release of proteoglycans by 110% (P < 0.001) and the production of MMP‐1 mRNA by 200% (P = 0.028). In addition, OA FLS produced 240% more MMP‐1 when stimulated with glycated albumin (P < 0.001). Glycated matrix or albumin increased the catabolic activity of OA FLS, which was assessed as invasive behavior, by 150% and 140% (P = 0.001 and P = 0.010), respectively. Effects of stimulation with AGEs were blocked by a neutralizing antibody against RAGE, but not by an isotype control.This study shows that AGEs trigger RAGE on chondrocytes and FLS, leading to increased catabolic activity and therefore to cartilage degradation. AGEs, via RAGE, could therefore contribute to the development and/or progression of OA. [ABSTRACT FROM AUTHOR]