BACKGROUND: Infrapatellar fat pad (IPFP) might be involved in osteoarthritis (OA) by production of cytokines. It was hypothesised that production of cytokines is sensitive to environmental conditions. OBJECTIVES: To evaluate cytokine production by IPFP in response to interleukin (IL)1β and investigate the ability to modulate this response with an agonist for peroxisome proliferator activated receptor α (PPARα), which is also activated by lipid-lowering drugs such as fibrates. METHODS: Cytokine secretion of IPFP was analysed in the medium of explant cultures of 29 osteoarthritic patients. IPFP (five donors) and synovium (six donors) were cultured with IL-1β and PPARα agonist Wy14643. Gene expression of IL-1β, monocyte chemoattractant protein (MCP1), (IL-6, tumour necrosis factor (TNF)α, leptin, vascular endothelial growth factor (VEGF), IL-10, prostaglandin-endoperoxide synthase (PTGS)2 and release of TNFα, MCP1 and prostaglandin E(2) were compared with unstimulated IPFP and synovium explants. RESULTS: IPFP released large amounts of inflammatory cytokines, adipokines and growth factors. IL-1β increased gene expression of PTGS2, TNFα, IL-1β, IL-6 and VEGF and increased TNFα release in IPFP. MCP1, leptin, IL-10 gene expression and MCP1, leptin and PGE(2) release did not increase significantly. Synovium responded to IL-1β similarly to IPFP, except for VEGF gene expression. Wy14643 decreased gene expression of PTGS2, IL-1β, TNFα, MCP1, VEGF and leptin in IPFP explants and IL-1β, TNFα, IL-6, IL-10 and VEGF in synovium that responded to IL-1β. CONCLUSION: IPFP is an active tissue within the joint. IPFP cytokine production is increased by IL-1β and decreased by a PPARα agonist. The effects were similar to effects seen in synovium. Fibrates may represent a potential disease-modifying drug for OA by modulating inflammatory properties of IPFP and synovium.
BACKGROUND: Infrapatellar fat pad (IPFP) might be involved in osteoarthritis (OA) by production of cytokines. It was hypothesised that production of cytokines is sensitive to environmental conditions. OBJECTIVES: To evaluate cytokine production by IPFP in response to interleukin (IL)1β and investigate the ability to modulate this response with an agonist for peroxisome proliferator activated receptor α (PPARα), which is also activated by lipid-lowering drugs such as fibrates. METHODS: Cytokine secretion of IPFP was analysed in the medium of explant cultures of 29 osteoarthritic patients. IPFP (five donors) and synovium (six donors) were cultured with IL-1β and PPARα agonist Wy14643. Gene expression of IL-1β, monocyte chemoattractant protein (MCP1), (IL-6, tumour necrosis factor (TNF)α, leptin, vascular endothelial growth factor (VEGF), IL-10, prostaglandin-endoperoxide synthase (PTGS)2 and release of TNFα, MCP1 and prostaglandin E(2) were compared with unstimulated IPFP and synovium explants. RESULTS: IPFP released large amounts of inflammatory cytokines, adipokines and growth factors. IL-1β increased gene expression of PTGS2, TNFα, IL-1β, IL-6 and VEGF and increased TNFα release in IPFP. MCP1, leptin, IL-10 gene expression and MCP1, leptin and PGE(2) release did not increase significantly. Synovium responded to IL-1β similarly to IPFP, except for VEGF gene expression. Wy14643 decreased gene expression of PTGS2, IL-1β, TNFα, MCP1, VEGF and leptin in IPFP explants and IL-1β, TNFα, IL-6, IL-10 and VEGF in synovium that responded to IL-1β. CONCLUSION: IPFP is an active tissue within the joint. IPFP cytokine production is increased by IL-1β and decreased by a PPARα agonist. The effects were similar to effects seen in synovium. Fibrates may represent a potential disease-modifying drug for OA by modulating inflammatory properties of IPFP and synovium.
Authors: Nathan M Solbak; Bryan J Heard; Yamini Achari; May Chung; Nigel G Shrive; Cyril B Frank; David A Hart Journal: Inflamm Res Date: 2015-06-20 Impact factor: 4.575
Authors: A Batushansky; S Zhu; R K Komaravolu; S South; P Mehta-D'souza; T M Griffin Journal: Osteoarthritis Cartilage Date: 2021-09-17 Impact factor: 6.576
Authors: Y M Bastiaansen-Jenniskens; M Siawash; C H A van de Lest; J A N Verhaar; M Kloppenburg; A-M Zuurmond; V Stojanovic-Susulic; G J V M Van Osch; S Clockaerts Journal: Cartilage Date: 2013-10 Impact factor: 4.634