Characterization of intra-articular adipose tissue from osteoarthritis knee and hip and involvement of infrapatellar fat pad, the main adipose tissue of the knee joint, in the pathophysiology of osteoarthritis

Les tissus adipeux (TA) intra-articulaires (TAIA) sont présents dans la majorité des articulations, au contact de la membrane synoviale. Le genou est l'articulation la plus riche en TA, comprenant le TA de Hoffa (TAH) et les TA suprapatellaires (TASP). A l'inverse, la hanche ne comprend qu'un petit TA, le TA acétabulaire (TAA). Le TAH de sujets arthrosiques est une source plus importante de cytokines inflammatoires que les TA sous-cutanés (TASC). Nous émettons l'hypothèse que les cytokines sécrétées par les TAH modifient le phénotype de la membrane synoviale arthrosique et que l'ensemble des TAIA partage des caractéristiques histologiques et biologiques communes les distinguant des TASC. Nous avons d'abord montré que la stimulation par les milieux conditionnés de TAH autologues induisait une expression et une libération plus importantes d'IL-6, d'IL-8, de PGE2, de MMP-1, de MMP-3 et de MMP-9 par les synoviocytes fibroblastiques (SF) comparativement aux TASC. La PGE2, sécrétée en plus grande quantité par les TAIA que les TASC (75 fois plus), joue un rôle central dans l'activation des SF. A l'instar des TAH, les autres TAIA de genou et de hanche sécrétent également plus de médiateurs inflammatoires que les TASC. Ils sont le siège de plus de remaniements fibreux, de vaisseaux et d'infiltrats leucocytaires que les TASC. Au sein des TAIA, les adipocytes sont plus petits et l'expression génique des médiateurs du métabolisme lipidique (ATGL, LPL, FABP4 et CD36) diminuée. Les TAIA de genou et de hanche arthrosiques partagent donc un phénotype commun et ont la capacité d'interagir avec la membrane synoviale, pouvant ainsi contribuer à la maladie arthrosique.Intra-articular adipose tissues (IAAT) are located in most joints, lined by synovial membrane. IAAT within the knee are the most numerous and voluminous. They are principally constituted by the infrapatellar fat pad (IFP) and suprapatellar fat pad (SPFP). Inversely, the hip is only constituted by a small single AT, called acetabular fat pad (AFP). Moreover, several studies brought out that IFP from OA patients were a greater source of inflammatory cytokines as compared to subcutaneous AT (SCAT). So, we hypothesized that cytokines released by IFP could modify the phenotype of synovial membrane and also that all IAAT share similar histological, biological and cellular characteristics distinguishing them from SCAT. First, we showed that synoviocyte stimulation by autologous IFP-conditioned media induced a higher gene expression and release of IL-6, IL-8, PGE2, MMP-1, MMP-3 and MMP-9 as compared to SCAT. We also confirmed that IFP released higher rate of inflammatory cytokines than SCAT, particularly PGE2, whom secretion rate was 75 fold higher and which had a central impact in synoviocyte activation. Next, we demonstrated that other IAAT from knee and hip also released higher levels of IL-6, IL-8, and PGE2 as compared to SCAT. IAAT were composed by greater fibrosis remodeling and higher vessel area and leucocyte infiltration as compared to autologous SCAT. In IAAT, adipocytes were smaller and gene expression for most factors involved in lipid metabolism (ATGL, LPL, FABP4 et CD36) were decreased. The specificity of inflammatory secretion and metabolic phenotype were also observed in preadipocytes isolated from knee IAAT and SCAT. To conclude, IAAT from OA knee and hip share a common phenotype and have the ability to interact with synovial membrane, contributing to the onset and/or the progression of OA disease