Induction of an Inflammatory and Prodegradative Phenotype in Autologous Fibroblast-like Synoviocytes by the Infrapatellar Fat Pad From Patients With Knee Osteoarthritis

Objective. The infrapatellar fat pad (IFP) of the knee joint has an inflammatory phenotype in osteoarthritis (OA). Its close proximity to the synovial membrane suggests that the IFP could be involved in the induction of OA synovitis. This study was undertaken to investigate the response of fibroblast-like synoviocytes (FLS) to autologous IFP and subcutaneous adipose tissue (SCAT) from patients with severe knee OA. Methods. Samples of IFP, SCAT, and autologous synovial membrane tissue close to the IFP were harvested during surgery from 28 patients with end-stage knee OA. FLS from 14 patients were stimulated with autologous IFP- or SCAT-conditioned medium, and levels of messenger RNA (mRNA) expression and protein release of interleukin-6 (IL-6), IL-8, secretory phospholipase A(2) (sPLA(2)), cytosolic PLA(2), cyclooxygenase 2 (COX-2), microsomal prostaglandin E synthase, prostaglandin E-2 (PGE(2)), and matrix metalloproteinases (MMPs) 1, 3, 9, and 13 were evaluated. Both IFP- and SCAT-conditioned medium were evaluated by enzyme-linked immunosorbent assay for secretion of IL-6, soluble IL-6 receptor (sIL-6R), IL-8, tumor necrosis factor alpha (TNF alpha), PGE(2), IL-1 beta, and interferon-gamma. In addition, OA FLS were treated with PGE(2) receptor antagonists to evaluate the contribution of IFP-derived PGE(2) to the inflammatory response of FLS to the IFP. Results. Stimulation of OA FLS with IFP-conditioned medium induced the mRNA expression and protein release of IL-6, IL-8, sPLA(2), COX-2, PGE(2), and MMPs 1, 3, 9, and 13. The extent of stimulation was consistently stronger with IFP-conditioned medium than with SCAT-conditioned medium. Moreover, secretion of IL-6, sIL-6R, IL-8, TNF alpha, and PGE(2) was greater in IFP-conditioned medium than in SCAT-conditioned medium, especially PGE(2), whose secretion was 75-fold stronger in IFP-conditioned medium (P < 0.0001). PGE(2) receptor antagonists dose-dependently inhibited the release of IL-6, IL-8, and PGE(2) by IFP-stimulated FLS. Conclusion. This study showed that the IFP has a potential role in the induction of synovial inflammation in patients with severe knee OA. Furthermore, secretion of PGE(2) by the IFP may be involved in the OA inflammatory process.