The Infrapatellar Fat Pad in Knee Osteoarthritis An Important Source of Interleukin-6 and Its Soluble Receptor

INSERM UMR-S 747, Université Paris Descartes, Paris, France.
Arthritis & Rheumatology (Impact Factor: 7.76). 11/2009; 60(11):3374-7. DOI: 10.1002/art.24881
Source: PubMed


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.

Download full-text


Available from: Xavier Chevalier, May 26, 2015
  • Source
    • "Alternatively, EAT from patients with cardiovascular disease might be exposed to proinflammatory cytokines (Ohsumi et al., 1994), which are able to inhibit adipogenesis and block the insulin action in adipocytes and preadipocytes (Lumeng et al., 2007). Finally, another important explanation of the lower EAT-MCs adipogenic ability might be due to an increase in mitochondrial biogenesis and fatty acid oxidation because we found an increase of UCP-1 expression levels in EAT-MCs after adipogenesis induction (Supplementary Fig. S3), as it was described in Zucker rats (Distel et al., 2009). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The thickness of epicardial adipose tissue (EAT), which is an inflammatory source for coronary artery disease (CAD), correlates with insulin resistance. One trigger factor is impaired adipogenesis. Here, our aim was to clarify the underlying mechanisms of insulin resistance on EAT-mesenchymal cells (MC). EAT and subcutaneous adipose tissue (SAT) were collected from 19 patients who were undergoing heart surgery. Their dedifferentiated adipocytes (DAs) and/or MCs were cultured. After the induction of adipogenesis or stimulation with insulin, the expression of adipokines was analyzed using real-time polymerase chain reaction (PCR). Colorimetric assays were performed to measure glucose levels and proliferation rate. Proteins modifications were detected via the proteomic approach and Western blot. Our results showed lower adipogenic ability in EAT-MCs than in SAT-MCs. Maximum adiponectin levels were reached within 28–35 days of exposure to adipogenic inducers. Moreover, the adipogenesis profile in EAT-MCs was dependent on the patients' clinical characteristics. The low adipogenic ability of EAT-MCs might be associated with an insulin-resistant state because chronic insulin treatment reduced the inflammatory cytokine expression levels, improved the glucose consumption, and increased the post-translational modifications (PTMs) of the glycolytic enzyme phosphoglycerate mutase 1 (PGAM1). We found lower adipogenic ability in EAT-MCs than in SAT-MCs. This lower ability level was dependent on gender and the presence of diabetes, obesity, and CAD. Low adipogenesis ability and insulin resistance in EAT-MCs might shed light on the association between EAT dysfunction and cardiovascular disease. J. Cell. Physiol. © 2014 Wiley Periodicals, Inc.
    Full-text · Article · Nov 2014 · Journal of Cellular Physiology
  • Source
    • "IL-6 is a glycoprotein consisting of 184 amino acid residues, which in the process of posttranslational processing ultimately becomes an interconnected structure of four α-helices [97]. The production of IL-6 in the tissues of the affected joint is usually in response to IL-1β and TNFα and is mainly implemented by chondrocytes, osteoblasts, FLS, macrophages, and adipocytes [39, 98–102]. The increased concentration of IL-6 is present in both the synovial fluid and serum and is positively correlated with the intensity of lesions in X-ray imaging [103–107]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Osteoarthritis (OA) is the most common chronic disease of human joints. The basis of pathologic changes involves all the tissues forming the joint; already, at an early stage, it has the nature of inflammation with varying degrees of severity. An analysis of the complex relationships indicates that the processes taking place inside the joint are not merely a set that (seemingly) only includes catabolic effects. Apart from them, anti-inflammatory anabolic processes also occur continually. These phenomena are driven by various mediators, of which the key role is attributed to the interactions within the cytokine network. The most important group controlling the disease seems to be inflammatory cytokines, including IL-1 β , TNF α , IL-6, IL-15, IL-17, and IL-18. The second group with antagonistic effect is formed by cytokines known as anti-inflammatory cytokines such as IL-4, IL-10, and IL-13. The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of OA with respect to inter- and intracellular signaling pathways is still under investigation. This paper summarizes the current state of knowledge. The cytokine network in OA is put in the context of cells involved in this degenerative joint disease. The possibilities for further implementation of new therapeutic strategies in OA are also pointed.
    Full-text · Article · Apr 2014 · Mediators of Inflammation
  • Source
    • "As these cytokines were also detected in synovial fluid of the same patients, these data are the first to indicate that IFP could be a source of cytokines/chemokines in the knee joint. Later studies showed more directly that IFP actively secretes IL-6 and its soluble receptor, sIL-6R, at higher levels than sc adipose tissue from the same patients [31] and showed secretion of TNFα and various adipokines from this tissue [32]. Adipokines have long been believed to be cytokines secreted specifically by adipose tissue (hence their name). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The role of inflammation in the development, progression, and clinical features of osteoarthritis has become an area of intense research in recent years. This led to the recognition of synovitis as an important source of inflammation in the joint and indicated that synovitis is intimately associated with pain and osteoarthritis progression. In this review, we discuss another emerging source of inflammation that could play a role in disease development/progression: the infrapatellar fat pad (IFP). The aim of this review is to offer a comprehensive view of the pathology of IFP as obtained from magnetic resonance studies, along with its characterization at both the cellular and the molecular level. Furthermore, we discuss the possible function of this organ in the pathological processes in the knee by summarizing the knowledge regarding the interactions between IFP and other joint tissues and discussing the pro- versus anti-inflammatory functions this tissue could have. We hope that this review will offer an overview of all published data regarding the IFP and will indicate novel directions for future research.
    Full-text · Article · Dec 2013 · Arthritis research & therapy
Show more