The Infrapatellar Fat Pad in Knee Osteoarthritis An Important Source of Interleukin-6 and Its Soluble Receptor
Obesity is a potent risk factor in knee osteoarthritis (OA). It has been suggested that adipokines, secreted by adipose tissue (AT) and largely found in the synovial fluid of OA patients, derive in part from the infrapatellar fat pad (IFP), also known as Hoffa's fat pad. The goal of this study was to characterize IFP tissue in obese OA patients and to compare its features with thigh subcutaneous AT to determine whether the IFP contributes to local inflammation in knee OA via production of specific cytokines. IFP and subcutaneous AT samples were obtained from 11 obese women (body mass index > or =30 kg/m2) with knee femorotibial OA. Gene expression was measured by real-time quantitative polymerase chain reaction. Cytokine concentrations in plasma and in conditioned media of cultured AT explants were determined by enzyme-linked immunosorbent assay or by Luminex xMAP technology. In IFP tissue versus subcutaneous AT, there was a decrease in the expression of genes for key enzymes implicated in adipocyte lipid metabolism, whereas the expression levels of genes for AT markers remained similar. A 2-fold increase in the expression of the gene for interleukin-6 (IL-6), a 2-fold increase in the release of IL-6, and a 3.6-fold increase in the release of soluble IL-6 receptor (sIL-6R) were observed in IFP samples, compared with subcutaneous AT, but the rates of secretion of other cytokines in IFP samples were similar to the rates in subcutaneous AT. In addition, leptin secretion was decreased by 40%, whereas adiponectin secretion was increased by 70%, in IFP samples versus subcutaneous AT. Our results indicate that the IFP cytokine profile typically found in OA patients could play a role in paracrine inflammation via the local production of IL-6/sIL-6R and that such a profile might contribute to damage in adjacent cartilage.
[Show abstract] [Hide abstract] ABSTRACT: Emerging data suggest that several metabolic factors, released mainly by white adipose tissue (WAT) and joint tissues, and collectively named adipokines, might have a role in the pathophysiology of OA. Recently, novel adipokines such as SERPINE2, WISP2, GPNMB and ITIH5 have been identified in WAT. The main goal of this study was to analyse the expression of these novel adipokines in synovium, infrapatellar fat pad and chondrocytes and to compare the expression of these molecules in healthy and OA tissues. Synovial tissues, infrapatellar fat pad and chondrocytes were obtained from 36 OA patients (age 52-85; mean BMI 28.9) who underwent total knee replacement surgery. Healthy synovial tissues and infrapatellar fat pad were obtained from 15 traumatic knee patients (age 23-53; mean BMI 23.5). mRNA and protein expression were determined by qRT-PCR and western blot analysis respectively. All the novel adipokines, matter of our study, are expressed in OA synovium, infrapatellar fat pad and chondrocytes. Moreover, we detected a differential expression of SERPINE2 and ITIH5 in OA synovial tissues as compared to healthy samples. Finally, we also observed an increased expression of WISP2 in OA infrapatellar fat pad in comparison to healthy controls. In this study we demonstrated for the first time the expression of four novel adipokines in different joint tissues and how these molecules are differentially expressed in healthy and OA joint tissues.
- "For instance, leptin and chemerin, positively correlated with the severity of osteoarthritis91011. Actually, the local production by joint tissues has been postulated as an important source of these adipokines as well as other inflammatory mediators [9,121314. Therefore, the alteration of their secretion pattern during OA could impact cartilage and synovium homeostasis. In fact, IPFPs and synovial fibroblasts, exposed to pro-inflammatory cytokines such as IL-1β, released large amounts of pro-inflammatory mediators, including prostaglandinE 2 , TNF-α or IL-6, and adipokines such as leptin . "
[Show abstract] [Hide abstract] ABSTRACT: Osteoarthritis (OA) is one of the most common causes of musculoskeletal disability in the world. Traditionally, it has been thought that obesity contributes to the development and progression of OA by increased mechanical load of the joint structures. Nevertheless, studies have shown that adipose tissue-derived cytokines (adipocytokines) are a possible link between obesity and OA. Furthermore, according to recent findings, not only articular cartilage may be the main target of these cytokines but also the synovial membrane, subchondral bone and infrapatellar fat pad may be encompassed in the process of degradation. This review presents the most recent reports on the contribution of adipocytokines to the knee joint cartilage degradation, osteophyte formation, infrapatellar fat pad alterations and synovitis.
- "When the subcutaneous fat tissue (SCFT) and fat pad tissue (FPT)-derived cells were compared, IPFP adipocytes showed a twofold increase in IL-6 gene expression and in IL-6 release. Interestingly, leptin secretion was 40 % lower and adiponectin was increased by 70 % in IPFP cells compared with the subcutaneous adipose tissue  . Moreover, it was demonstrated that the culture media from OA patients' IPFP adipocytes induced MMP13 and MMP1 expression in articular chondrocytes and that the leptin level positively correlated with the expression of both MMPs and cartilage collagen de- struction . "
- "Indeed, genes contributing to an inflammatory joint state were in general not highly differentially expressed between IFP and SAT among those with endstage OA, In other words, SAT gene expression was more similar to that of IFP among those with later stage disease. In the only other previous work comparing IFP to SAT fat samples, Distal et al.  studied differences in gene expression between IFP and SAT among individuals with endstage knee OA. Consistent with our findings, the authors reported that the majority of cytokines demonstrated similar expressions between the two adipose tissues, with only small fold increases in IL-6 and IL-6 receptor (2 to 3 fold) in IFP tissue and decreased expression of genes related to lipid metabolism in SAT. "