Association between weight or Body Mass Index and hand osteoarthritis: a systematic review

Objective: To investigate the association between weight or Body Mass Index (BMI) and the development of hand osteoarthritis (OA). Methods: Systematic review of observational studies. Medical databases were searched up to April 2008. Articles which presented data on the association between weight and hand OA were selected. The qualities of these studies were then assessed by two independent reviewers using a 19 criteria scoring syst

Monounsaturated and Saturated, but Not n-6 Polyunsaturated Fatty Acids Decrease Cartilage Destruction under Inflammatory Conditions

Purpose: Osteoarthritis (OA) is associated with obesity in which altered fatty acid levels have been observed. We investigated whether the most common fatty acids in synovial fluid influence cartilage deterioration in OA. Design: Cartilage was obtained from OA patients undergoing total knee arthroplasty. Chondrocytes or cartilage explants were cultured with linoleic (n-6 polyunsaturated), oleic (monounsaturated), or palmitic (saturated) acid. After preculture, media were renewed and inflammation was simulated in half of the samples by addition of 10 ng/mL tumor necrosis factor-\xce\xb1 (TNF\xce\xb1) with or without the fatty acids. Effects on lipid uptake (Oil-Red-O), cell toxicity (lactate dehydrogenase), prostaglandin-E2 (PGE2) release and gene expression for prostaglandin-endoperoxide synthase-2 (PTGS2), matrix metalloproteinase-1 (MMP1), and MMP13, and a disintegrin and metalloproteinase with thrombospondin motifs 4 were determined on chondrocytes in monolayer. Effects on glycosaminoglycan (GAG) release were evaluated on cartilage explants. Results: None of the fatty acids were cytotoxic and all were taken up by the cells, resulting in a higher amount of intracellular lipid in chondrocytes. Linoleic acid increased PGE2 production in the presence of TNF\xce\xb1. Oleic acid and palmitic acid inhibited MMP1 gene expression in chondrocytes stimulated with TNF\xce\xb1. In cartilage explants, GAG release was also inhibited by oleic acid and palmitic acid, and oleic acid decreased PTGS2 gene expression in stimulated chondrocytes. Conclusions: Linoleic acid has a pro-inflammatory effect on cartilage whereas oleic acid and palmitic acid seem to inhibit cartilage destruction. These results indicate that altered fatty acid levels may influence loss of cartilage structure in OA

Inflammatory Cells in Patients with Endstage Knee Osteoarthritis: A Comparison between the Synovium and the Infrapatellar Fat Pad

OBJECTIVE: To get a better understanding of inflammatory pathways active in the osteoarthritic (OA) joint, we characterized and compared inflammatory cells in the synovium and the infrapatellar fat pad (IFP) of patients with knee OA. METHODS: Infiltrating immune cells were characterized by flow cytometry in 76 patients with knee OA (mean age 63.3, 52% women, median body mass index 28.9) from whom synovial tissue (n = 40) and IFP (n = 68) samples were obtained. Pain was assessed by the visual analog scale (VAS; 0-100 mm). Spearman rank correlations and linear regression analyses adjusted for sex and age were performed. RESULTS: Macrophages and T cells, followed by mast cells, were the most predominant immune cells in the synovium and IFP, and were equally abundant in these tissues. Macrophages and T cells secreted mostly proinflammatory cytokines even without additional stimulation, indicating their activated state. Accordingly, most CD4+ T cells had a memory phenotype and contained a significant population of cells expressing activation markers (CD25+, CD69+). Interestingly, the percent of CD69+ T cells was higher in synovial than IFP CD4+ T cells. Preliminary analyses indicated that the number of synovial CD4+ T cells were associated with VAS pain (β 0.51, 95% CI 0.09-1.02, p = 0.02). CONCLUSION: Our data suggest that the immune cell composition of the synovium and the IFP is similar, and includes activated cells that could contribute to inflammation through secretion of proinflammatory cytokines. Moreover, preliminary analyses indicate that synovial CD4+ T cells might associate with pain in patients with endstage OA of the knee

Soluble mediator secretion by non-stimulated and stimulated synovial tissue explants (STEs) from normal and OA donors.

<p>Graphs demonstrate the absolute levels of all soluble mediators, which were significantly (p<0.01) different between <b>A.</b> non-stimulated (black bars) and IL-1α-stimulated (white bars) normal STEs and <b>B.</b> non-stimulated (grey bars) and IL-1α-stimulated (white bars) OA STEs. Data were obtained from pooled supernatants representing the average of 6 STEs per donor and the production in a time period of 7 days. Data are plotted on a log scale. Bars indicate mean concentration (pg/ml culture medium) ± SD.</p

Percentage GAG release from cartilage explants cultured alone or together with STEs under non-stimulated and IL-1α-stimulated conditions.

<p>%GAG release is indicated as mean (SD).</p><p>Δ STE+cartilage: corrected value for GAG release in the cartilage explant.</p

Secreted MMP activity (rfu/sec) by STE and cartilage alone and by the co-culture of STE and cartilage under non-stimulated and Il-1α-stimulated conditions.

<p>Secreted MMP activity is indicated as mean (SD).</p

Proteoglycan degradation of healthy cartilage explants cultured alone or together with synovial tissue explants (STEs).

<p>Proteoglycan degradation was expressed as the percentage of glycosaminoglycans (GAG) released into the medium during 7 days of culture of cartilage alone or co-cultured together with normal (<b>A, B</b>) or OA (<b>C, D</b>) STEs without (<b>A, C</b>) or with (<b>B, D</b>) IL-1α stimulation. Each line represents an individual donor and connects the % GAG release of cartilage alone (left) with the matching co-culture condition of cartilage together with STEs (right). There were no significant differences between cartilage cultured alone or co-cultured with normal or OA STEs.</p

Soluble mediator secretion by normal and OA synovial tissue explants (STEs) with or without IL-1α.

<p>Graphs demonstrate all soluble mediators which were significantly (p<0.01) different between <b>A.</b> normal (black bars) and OA (grey bars) STEs and <b>B.</b> normal and OA STEs under pro-inflammatory (IL-1α) conditions. Data were obtained from pooled supernatants representing the average of 6 STEs per donor and the production in a time period of 7 days. Data are plotted on a log scale. Bars indicate mean concentration (pg/ml culture medium) ± SD.</p

Adipocytes Modulate the Phenotype of Human Macrophages through Secreted Lipids

Previous studies have shown accumulation and an enhanced proinflammatory profile of macrophages in adipose tissue of obese mice, indicating the presence of an interaction between adipocytes and macrophages in this tissue. However, the consequences of this interaction in humans are yet incompletely understood. In this study, we explored the modulating effects of adipocytes on the phenotype of macrophages in humans and studied the possible molecular pathways involved. Adipocyte-conditioned media (ACM) treatment of macrophages for 48 h strongly reduced the LPS-induced IL-12p40 secretion by macrophages, whereas the production of TNF-α and other cytokines remained largely unaffected. This effect was independent of the source of adipocytes. Interestingly, the level of inhibition correlated directly with body mass index (BMI) of the adipocyte donor. Because adipocytes release many different cytokines, adipokines, and lipids, we have separated the protein and lipid fractions of ACM, to obtain insight into the molecular nature of the soluble mediators underlying the observed effect. These experiments revealed that the inhibitory effect resided predominantly in the lipid fraction. Further studies revealed that PGE2 and linoleic and oleic acid were potent inhibitors of IL-12p40 secretion. Interestingly, concentrations of these ACM-derived lipids increased with increase in BMI of the adipocyte donor, suggesting that they could mediate the BMI-dependent effects of ACM. To our knowledge, these results provide first evidence that obesity-related changes in adipose tissue macrophage phenotype could be mediated by adipocyte-derived lipids in humans. Intriguingly, these changes appear to be different from those in murine obesity