INSERM, Sorbonne University, UPMC Univ Paris 06, Centre de Recherche Saint-Antoine (CRSA), Paris, France.
Department of Rheumatology, AP-HP Henri Mondor Hospital, Créteil Cedex, France.
Ann Rheum Dis. 2017 Jun;76(6):1142-1148. doi: 10.1136/annrheumdis-2016-210478. Epub 2017 Mar 15.
Compared with subcutaneous adipose tissue (SCAT), infrapatellar fat pad (IFP), the main knee intra-articular adipose tissue (IAAT), has an inflammatory phenotype in patients with osteoarthritis (OA). We phenotyped suprapatellar fat pad (SPFP) and hip acetabular fat pad (AFP), two other IAATs, to determinate the unique signature of IAATs compared with SCAT.
IFP, SPFP, AFP and autologous SCAT were obtained from patients with OA during total knee (n=38) or hip replacement (n=5). Fibrosis and adipocyte area were analysed by histology and vascularisation, leucocyte and mast cell infiltration were analysed by immunohistochemistry for von Willebrand factor, leucocytes and tryptase, respectively. Secretion of interleukin (IL)-6, IL-8 and prostaglandin E (PGE) was assessed by ELISA. The mRNA expression of adipocyte-associated genes (ATGL, LPL, PPAR-γ, FABP4 and CD36) and developmental genes (SFRP2, HoxC9 and EN1) was determined. The inflammatory response of isolated fibroblast-like synoviocytes (FLS) to autologous IFP and SPFP conditioned media was examined.
Fibrosis, vascularisation and leucocyte and mast cell infiltration were greater in IAATs than SCAT, and levels of IL-6, IL-8 and PGE were greater in all IAATs than SCAT. IFP and SPFP induced a similar inflammatory response to FLS. Adipocyte area was smaller in IAATs than SCAT. Adipocyte-associated and developmental genes showed a similar gene expression pattern in all IAATs, different from SCAT.
IFP but also SPFP and AFP (gathered under the term 'IAAT') may play a deleterious role in OA by affecting joint homeostasis because of their inflammatory phenotype and their close interaction with synovium in the same functional unit.
与皮下脂肪组织(SCAT)相比,髌下脂肪垫(IFP)作为膝关节主要关节内脂肪组织(IAAT),在骨关节炎(OA)患者中具有炎症表型。我们对髌上脂肪垫(SPFP)和髋关节髋臼脂肪垫(AFP)这两种其他 IAAT 进行表型分析,以确定 IAAT 与 SCAT 相比的独特特征。
在全膝关节(n=38)或髋关节置换术(n=5)过程中,从 OA 患者中获得 IFP、SPFP、AFP 和自体 SCAT。通过组织学分析纤维化和脂肪细胞面积,通过免疫组织化学分别针对血管性血友病因子、白细胞和胰蛋白酶检测血管化、白细胞和肥大细胞浸润。通过 ELISA 评估白细胞介素(IL)-6、IL-8 和前列腺素 E(PGE)的分泌。测定脂肪细胞相关基因(ATGL、LPL、PPAR-γ、FABP4 和 CD36)和发育基因(SFRP2、HoxC9 和 EN1)的 mRNA 表达。检查自体 IFP 和 SPFP 条件培养基对分离的成纤维样滑膜细胞(FLS)的炎症反应。
IAAT 中的纤维化、血管化以及白细胞和肥大细胞浸润均高于 SCAT,所有 IAAT 中的 IL-6、IL-8 和 PGE 水平均高于 SCAT。IFP 和 SPFP 诱导 FLS 产生相似的炎症反应。IAAT 中的脂肪细胞面积小于 SCAT。与 SCAT 相比,所有 IAAT 中的脂肪细胞相关和发育基因表达模式均相似。
IFP 以及 SPFP 和 AFP(统称为“IAAT”)可能通过其炎症表型及其与同一功能单元中滑膜的密切相互作用,对 OA 产生有害作用,从而影响关节内稳态。