ABSTRACT
BACKGROUND: Accumulation of advanced glycation end-products (AGEs) is involved in age-related osteoarthritis (OA). Glyoxalase (Glo)-1 is the main enzyme involved in the removal of AGE precursors, especially carboxymethyl-lysine (CML). We aimed to investigate the expression of several AGEs and Glo-1 in human OA cartilage and to study chondrocytic Glo-1 regulation by inflammation, mediated by interleukin (IL)-1ß. METHODS: Ex vivo, we quantified AGEs (pentosidine, CML, methylglyoxal-hydroimidazolone-1) in knee cartilage from 30 OA patients. Explants were also incubated with and without IL-1ß, and we assessed Glo-1 protein expression and enzymatic activity. In vitro, primary cultured murine chondrocytes were stimulated with increasing concentrations of IL-1ß to assess Glo-1 enzymatic activity and expression. To investigate the role of oxidative stress in the IL-1ß effect, cells were also treated with inhibitors of mitochondrial oxidative stress or nitric oxide synthase. RESULTS: Ex vivo, only the human cartilage CML content was correlated with patient age (r = 0.78, p = 0.0031). No statistically significant correlation was found between Glo-1 protein expression and enzymatic activity in human cartilage and patient age. We observed that cartilage explant stimulation with IL-1ß decreased Glo-1 protein expression and enzymatic activity. In vitro, we observed a dose-dependent decrease in Glo-1 mRNA, protein quantity, and enzymatic activity in response to IL-1ß in murine chondrocytes. Inhibitors of oxidative stress blunted this downregulation. CONCLUSION: Glo-1 is impaired by inflammation mediated by IL-1ß in chondrocytes through oxidative stress pathways and may explain age-dependent accumulation of the AGE CML in OA cartilage.
Subject(s)
Aging/metabolism , Glycation End Products, Advanced/metabolism , Inflammation Mediators/metabolism , Lactoylglutathione Lyase/biosynthesis , Osteoarthritis/metabolism , Age Factors , Aged , Aged, 80 and over , Aging/pathology , Animals , Cells, Cultured , Female , Humans , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Middle Aged , Osteoarthritis/pathologyABSTRACT
OBJECTIVES: The objective was to assess the efficacy of intra-articular injections of corticosteroids or hyaluronic acid in thumb osteoarthritis. METHODS: A systematic review of the literature was performed until August 2014. All controlled trials reporting the efficacy on pain, functional capacity and pulp pinch force of hyaluronic acid or corticosteroids in thumb osteoarthritis were selected. Pooled standardized response means (SRMs) were assessed by meta-analysis. RESULTS: Six trials were included and contributed to 3 meta-analyses (hyaluronic acid versus placebo, corticosteroids vs. placebo and hyaluronic acid vs. corticosteroids). Among the 428 patients included, 169 were treated with hyaluronic acid, 147 with corticosteroids and 74 with placebo. Versus placebo at week 12, hyaluronic acid (2 trials, 148 patients) lead to better functional capacity (SRM -1.14 [-1.69; -0.60]) with no difference on pain; corticosteroids (2 trials, 164 patients) lead to no difference on pain or function. When comparing hyaluronic acid vs. corticosteroids (4 trials, 304 patients), no difference was evidenced until week 12. At week 24, pain was significantly lower in the corticosteroids group (SRM 1.44 [0.14; 2.74]) and pulp pinch force higher in the hyaluronic acid group (SRM -0.75 [-3.87; -1.97]). CONCLUSION: This meta-analysis shows great heterogeneity. Hyaluronic acid may be useful to increase functional capacity and corticosteroids to decrease pain in thumb osteoarthritis at week 24.
