Microarray Analysis of the Infrapatellar Fat Pad in Knee Osteoarthritis: Relationship with Joint Inflammation
Microarray Analysis of the Infrapatellar Fat Pad in Knee Osteoarthritis: Relationship with Joint Inflammation
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DOI：
10.3899/jrheum.101302
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发表时间：
2011-09-01
影响因子：
3.9
通讯作者：
Mahomed, Nizar N.
中科院分区：
文献类型：
--
作者：
Gandhi, Rajiv;Takahashi, Mark;Mahomed, Nizar N.
目标。目的探讨终末期和早期膝关节骨关节炎（OA）髌下脂肪垫（IFP）中脂肪代谢、能量稳态、脂肪生成和炎症相关基因的差异。29例终末期和5例早期原发性OA IFP在膝关节手术中获得。提取总RNA，标记，并杂交到全基因组表达阵列。使用主成分分析或双向分层聚类对所有样本进行无监督分析，显示了基于组织来源和疾病的分组。统计测试确定了两种脂肪类型之间存在差异的几组基因。Western blot分析所鉴定的感兴趣基因的蛋白表达。29 IFP显示脂肪因子如脂联素和瘦素的表达升高。与对照组相比，在严重OA脂肪垫中，脂肪形成基因如过氧化物酶体增殖物激活受体γ (ppar - γ)、二酰基甘油酰基转移酶2 （DGAT2）、分化簇（CD36）和甲状腺激素反应点（THRSP）的表达有统计学意义上的显著增加。终末期OA组中5例患者的基因表达与早期OA组织一致。晚期OA组织中ppar - γ 2和ppar - γ 1的表达分别是早期OA组织的5.4倍和1.4倍。终末期OA脂肪垫表现出脂肪代谢和能量稳态基因的显著上调，炎症细胞因子的结果好坏参半。（《风湿病杂志》2011年7月15日首次发布；doi:10.3899/ jrheumat. 101302）
Objective. To examine differences in genes involved in fat metabolism, energy homeostasis, adipogenesis, and inflammation between endstage and early-stage knee osteoarthritis (OA) infrapatellar fat pads (IFP).Methods. Twenty-nine endstage and 5 early-stage primary OA IFP were harvested at knee surgery. Total RNA was extracted, labeled, and hybridized to whole-genome expression arrays. Unsupervised analysis of all samples using principal components analysis or 2-way hierarchical clustering showed groupings based on tissue source and disease. Statistical testing identified sets of genes that displayed differences between the 2 fat types. Western blot analysis was performed for protein expression of an identified gene of interest.Results. The 29 IFP demonstrated an elevation in the expression of adipokines such as adiponectin and leptin. A statistically significant increased expression was seen for genes of adipogenesis, such as peroxisome proliferator-activated receptor-gamma (PPAR-gamma), diacylglycerol acyltransferase 2 (DGAT2), cluster of differentiation (CD36), and thyroid hormone responsive spot (THRSP) in the severe OA fat pads as compared to the controls. A subset of 5 patients in the endstage OA group were consistently similar in gene expression to early OA tissue. Protein expression of PPAR-gamma 2 was 5.4-fold and PPAR-gamma 1 was 1.4-fold greater in endstage versus early OA tissue.Conclusion. Endstage OA fat pads demonstrated a significant upregulation of genes for fat metabolism and energy homeostasis and a mixed result for inflammatory cytokines. (J Rheumatol First Release July 15 2011; doi:10.3899/jrheum.101302)