title: Microarray analysis of the infrapatellar fat pad in knee osteoarthritis: relationship with joint inflammation.
abstract: 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-γ (PPAR-γ), 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-γ2 was 5.4-fold and PPAR-γ1 was 1.4-fold greater in endstage versus early OA tissue.
  
  
  CONCLUSIONS
  Endstage OA fat pads demonstrated a significant upregulation of genes for fat metabolism and energy homeostasis and a mixed result for inflammatory cytokines.
authors.affiliation: Toronto Western Hospital, East Wing 1-439, 399 Bathurst Street, Toronto, Ontario M5T 2S8, Canada. rajiv.gandhi@uhn.on.ca
authors.forename: Rajiv
authors.initials: R
authors.lastname: Gandhi
authors.forename: Mark
authors.initials: M
authors.lastname: Takahashi
authors.forename: Carl
authors.initials: C
authors.lastname: Virtanen
authors.forename: Khalid
authors.initials: K
authors.lastname: Syed
authors.forename: J Roderick
authors.initials: JR
authors.lastname: Davey
authors.forename: Nizar N
authors.initials: NN
authors.lastname: Mahomed
mesh_terms: D050156:Adipogenesis / Q000235:genetics; D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D004734:Energy Metabolism / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007719:Knee Joint / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D020370:Osteoarthritis, Knee / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*