Knee and hip intra-articular adipose tissues (IAATs) compared with autologous subcutaneous adipose tissue: a specific phenotype for a central player in osteoarthritis

Knee and hip intra-articular adipose tissues (IAATs) compared with autologous subcutaneous adipose tissue: a specific phenotype for a central player in osteoarthritis
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DOI:
10.1136/annrheumdis-2016-210478
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发表时间:
2017-06-01
影响因子:
27.4
通讯作者:
Houard, Xavier
Houard, Xavier
中科院分区:
医学1区
文献类型:
--
作者:
Eymard, Florent;Pigenet, Audrey;Houard, Xavier

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目的与皮下脂肪组织(SCAT)相比,髌下脂肪垫(IFP)是膝关节主要的关节内脂肪组织(IAAT),在骨关节炎(OA)患者中具有炎症表型。我们对另外两种iaat——髌上脂肪垫(SPFP)和髋臼脂肪垫(AFP)进行表型分析,以确定与SCAT相比iaat的独特特征。方法38例OA患者在全膝关节置换术(n=38)或人工髋关节置换术(n=5)中检测IFP、SPFP、AFP和自体SCAT。用组织学和血管化法分析纤维化和脂肪细胞面积,用免疫组化法分析白细胞和肥大细胞浸润,分别检测血管性血友病因子、白细胞和胰蛋白酶。ELISA法检测白细胞介素(IL)-6、IL-8、前列腺素E-2 (PGE(2))的分泌情况。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表达量。观察分离成纤维细胞样滑膜细胞(FLS)对自体IFP和SPFP条件培养基的炎症反应。结果iaat组纤维化、血管化、白细胞和肥大细胞浸润均高于SCAT组,IL-6、IL-8和PGE2水平均高于SCAT组。IFP和SPFP诱导的炎症反应与FLS相似。iaat组脂肪细胞面积小于SCAT组。脂肪细胞相关基因和发育基因在所有iaat中表现出相似的基因表达模式,与SCAT不同。结论IFP、SPFP和AFP(统称为“IAAT”)可能通过影响关节稳态在OA中发挥有害作用,因为它们的炎症表型以及它们在同一功能单元中与滑膜的密切相互作用。
Objectives 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.Methods 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-2 (PGE(2)) was assessed by ELISA. The mRNA expression of adipocyte-associated genes (ATGL, LPL, PPAR-gamma, 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.Results Fibrosis, vascularisation and leucocyte and mast cell infiltration were greater in IAATs than SCAT, and levels of IL-6, IL-8 and PGE2 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.Conclusions 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.