title: Proteomic analysis of synovial fluid from the osteoarthritic knee: comparison with transcriptome analyses of joint tissues.
abstract: OBJECTIVE
  The pathophysiology of the most common joint disease, osteoarthritis (OA), remains poorly understood. Since synovial fluid (SF) bathes joint cartilage and synovium, we reasoned that a comparative analysis of its protein constituents in health and OA could identify pathways involved in joint damage. We undertook this study to perform a proteomic analysis of knee SF from OA patients and control subjects and to compare the results to microarray expression data from cartilage and synovium.
  
  
  METHODS
  Age-matched knee SF samples from 10 control subjects, 10 patients with early-stage OA, and 10 patients with late-stage OA were compared using 2-dimensional difference-in-gel electrophoresis and mass spectrometry (MS). MS with a multiplexed peptide selected reaction monitoring assay was used to confirm differential expression of a subset of proteins in an independent OA patient cohort. Proteomic results were analyzed by Ingenuity Pathways Analysis and compared to published synovial tissue and cartilage messenger RNA profiles.
  
  
  RESULTS
  Sixty-six proteins were differentially present in healthy and OA SF. Three major pathways were identified among these proteins: the acute-phase response signaling pathway, the complement pathway, and the coagulation pathway. Differential expression of 5 proteins was confirmed by selected reaction monitoring assay. A focused analysis of transcripts corresponding to the differentially present proteins indicated that both synovial and cartilage tissues may contribute to the OA SF proteome.
  
  
  CONCLUSIONS
  Proteins involved in the acute-phase response signaling pathway, the complement pathway, and the coagulation pathway are differentially regulated in SF from OA patients, suggesting that they contribute to joint damage. Validation of these pathways and their utility as biomarkers or therapeutic targets in OA is warranted.
authors: Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors: Susan Y
authors: SY
authors: Ritter
authors: Roopashree
authors: R
authors: Subbaiah
authors: Gurkan
authors: G
authors: Bebek
authors: James
authors: J
authors: Crish
authors: Carla R
authors: CR
authors: Scanzello
authors: Bryan
authors: B
authors: Krastins
authors: David
authors: D
authors: Sarracino
authors: Mary F
authors: MF
authors: Lopez
authors: Mary K
authors: MK
authors: Crow
authors: Thomas
authors: T
authors: Aigner
authors: Mary B
authors: MB
authors: Goldring
authors: Steven R
authors: SR
authors: Goldring
authors: David M
authors: DM
authors: Lee
authors: Reuben
authors: R
authors: Gobezie
authors: Antonios O
authors: AO
authors: Aliprantis
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism; D000210:Acute-Phase Reaction / Q000378:metabolism; D000368:Aged; D001779:Blood Coagulation Factors / Q000235:genetics / Q000378:metabolism; D002356:Cartilage / Q000378:metabolism*; D016022:Case-Control Studies; D003165:Complement System Proteins / Q000235:genetics / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007719:Knee Joint / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000235:genetics / Q000378:metabolism*; D020543:Proteome / Q000032:analysis*; D012333:RNA, Messenger / Q000032:analysis*; D013582:Synovial Fluid / Q000737:chemistry / Q000378:metabolism*; D013583:Synovial Membrane / Q000378:metabolism*
chemical_list: D000209:Acute-Phase Proteins; D001779:Blood Coagulation Factors; D020543:Proteome; D012333:RNA, Messenger; D003165:Complement System Proteins
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