Knee and hip intra-articular adipose tissues share a common phenotype in osteoarthritis

Purpose: Infrapatellar fat pad (IFP), one of the three adipose tissues (AT) located into the knee is the subject of an increasing interest in the pathophysiology of osteoarthritis (OA). It differs from subcutaneous AT (SCAT) by a higher secretion of inflammatory mediators, induces a procatabolic phenotype on synoviocytes and chondrocytes, and can thus contribute to OA onset. To understand whether these features are specific to IFP or related to its intra-articular (IA) location, we compared the histologic features and the pattern of gene expression and cytokine release between two different knee IA AT [IFP and suprapatellar fat pad (SPFP)] and autologous SCAT but also between hip IA AT and SCAT. Methods: During arthroplasty for end-stage OA, samples of SPFP, IFP and SCAT from 38 patients and samples of hip IA AT and SCAT from 5 patients were harvested. Adipocytes were also isolated from 4 knee IA AT and SCAT. Secretion of IL-6, IL-8 and PGE2 was assessed by ELISA. The expression of genes involved in lipid metabolism (ATGL, LPL, PPAR-γ, FABP4 and CD36) and development (SFRP2, HoxC9 and EN1) was measured for each tissue but also for isolated adipocytes from knee AT. Adipocyte size and fibrotic remodelling were analysed on paraffin sections. Results: Secretion of IL-6, IL-8, and PGE2 was significantly greater in knee and hip IA AT-conditioned media as compared to autologous SCAT. Gene expression of most lipid metabolism mediators (ATGL, LPL, FABP4 and CD36) was decreased in IA AT. Same results were observed for isolated adipocytes from knee IA AT compared to SCAT. Among developmental gene, EN1 expression was significantly decreased in each IA AT whereas Hoxc9 was only repressed in SPFP and hip IA AT as compared with SCAT. Finally, fibrosis remodelling was greater in IA AT from knee and hip as compared with autologous SCAT whereas IA AT adipocyte had a smaller area than SCAT adipocyte. Conclusions: Knee and hip OA IA AT shared a common tissular phenotype including a less adipogenic profil but greater fibrotic and inflammatory characteristics as compared with autologous SCAT.