title: Genome wide gene expression analysis of the posterior capsule in patients with osteoarthritis and knee flexion contracture.
abstract: OBJECTIVE
  Knee flexion contractures (KFC) are limitations in the ability to fully extend the knee joint. In people with knee osteoarthritis (OA), KFC are common, impair function, and worsen outcomes after arthroplasty. In KFC, the posterior knee capsule is believed to play a key role, but the pathophysiology remains poorly understood. We sought to identify gene expression differences in the posterior knee capsule of patients with OA with and without KFC.
  
  
  METHODS
  Capsule tissue was obtained from the knees of 12 subjects diagnosed with advanced-stage OA at the time of knee arthroplasty surgery. The presence or absence of KFC allocated patients into 2 groups using a case-control design. Genomewide capsular gene expression was compared between the 2 patient groups. Confirmation of differential expression of the corresponding proteins was performed by immunohistochemistry on tissue sections.
  
  
  RESULTS
  There were no significant demographic differences between the patients with OA with KFC and without KFC save for reduced extension in their surgical knee (p<0.01). KFC patients showed a 6.4-fold decrease in CSN1S1 (p=0.017) gene expression and a 3.7-, 2.0-, and 2.6-fold increase in CHAD, Sox9, and Cyr61 gene expression, respectively (p=0.001, 0.004, 0.001, respectively). There were corresponding increases in protein levels for chondroadherin, sex determining region Y-box 9, and casein alphaS1 (all p<0.05). Functional analysis of the differentially expressed genes indicated a strong association with pathways related to the extracellular matrix and to tissue fibrosis.
  
  
  CONCLUSIONS
  Posterior capsules in endstage OA knees with KFC exhibited differential expression of 4 genes all previously documented to be associated with tissue fibrosis.
authors.affiliation: From the Department of Medicine, The Ottawa Hospital Rehabilitation Centre; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.T.M. Campbell, MD, MSc; G. Trudel, MD, MSc, Department of Medicine, The Ottawa Hospital Rehabilitation Centre, University of Ottawa; K.K. Wong, BSc; O. Laneuville, PhD, Department of Biochemistry, Microbiology and Immunology, University of Ottawa. tcampbell@bruyere.org.
authors.forename: Thomas Mark
authors.initials: TM
authors.lastname: Campbell
authors.affiliation: From the Department of Medicine, The Ottawa Hospital Rehabilitation Centre; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.T.M. Campbell, MD, MSc; G. Trudel, MD, MSc, Department of Medicine, The Ottawa Hospital Rehabilitation Centre, University of Ottawa; K.K. Wong, BSc; O. Laneuville, PhD, Department of Biochemistry, Microbiology and Immunology, University of Ottawa.
authors.forename: Guy
authors.initials: G
authors.lastname: Trudel
authors.affiliation: From the Department of Medicine, The Ottawa Hospital Rehabilitation Centre; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.T.M. Campbell, MD, MSc; G. Trudel, MD, MSc, Department of Medicine, The Ottawa Hospital Rehabilitation Centre, University of Ottawa; K.K. Wong, BSc; O. Laneuville, PhD, Department of Biochemistry, Microbiology and Immunology, University of Ottawa.
authors.forename: Kayleigh Kristin
authors.initials: KK
authors.lastname: Wong
authors.affiliation: From the Department of Medicine, The Ottawa Hospital Rehabilitation Centre; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.T.M. Campbell, MD, MSc; G. Trudel, MD, MSc, Department of Medicine, The Ottawa Hospital Rehabilitation Centre, University of Ottawa; K.K. Wong, BSc; O. Laneuville, PhD, Department of Biochemistry, Microbiology and Immunology, University of Ottawa.
authors.forename: Odette
authors.initials: O
authors.lastname: Laneuville
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002364:Caseins / Q000235:genetics / Q000378:metabolism; D015331:Cohort Studies; D003286:Contracture / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D006801:Humans; D017746:Joint Capsule / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020370:Osteoarthritis, Knee / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D010147:Pain Measurement; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D016059:Range of Motion, Articular / Q000502:physiology*; D055758:SOX9 Transcription Factor / Q000737:chemistry / Q000378:metabolism; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric
chemical_list: D002364:Caseins; D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; C088980:chondroadherin
keywords: CONTRACTURE; FIBROSIS; GENE EXPRESSION; MICROARRAY; OSTEOARTHRITIS