title: Diminished cartilage-lubricating ability of human osteoarthritic synovial fluid deficient in proteoglycan 4: Restoration through proteoglycan 4 supplementation.
abstract: OBJECTIVE
  The purposes of this study were 1) to quantify the proteoglycan 4 (PRG4) and hyaluronan (HA) content in synovial fluid (SF) from normal donors and from patients with chronic osteoarthritis (OA) and 2) to assess the cartilage boundary-lubricating ability of PRG4-deficient OA SF as compared to that of normal SF, with and without supplementation with PRG4 and/or HA.
  
  
  METHODS
  OA SF was aspirated from the knee joints of patients with symptomatic chronic knee OA prior to therapeutic injection. PRG4 concentrations were measured using a custom sandwich enzyme-linked immunosorbent assay (ELISA), and HA concentrations were measured using a commercially available ELISA. The molecular weight distribution of HA was measured by agarose gel electrophoresis. The cartilage boundary-lubricating ability of PRG4-deficient OA SF, PRG4-deficient OA SF supplemented with PRG4 and/or HA, and normal SF was assessed using a cartilage-on-cartilage friction test. Two friction coefficients (μ) were calculated: static (μ(static, Neq) ) and kinetic (<μ(kinetic, Neq) >) (where N(eq)  represents equilibrium axial load and angle brackets indicate that the value is an average).
  
  
  RESULTS
  The mean ± SEM PRG4 concentration in normal SF was 287.1 ± 31.8 μg/ml. OA SF samples deficient in PRG4 (146.5 ± 28.2 μg/ml) as compared to normal were identified and selected for lubrication testing. The HA concentration in PRG4-deficient OA SF (mean ± SEM 0.73 ± 0.08 mg/ml) was not significantly different from that in normal SF (0.54 ± 0.09 mg/ml). In PRG4-deficient OA SF, the molecular weight distribution of HA was shifted toward the lower range. The cartilage boundary-lubricating ability of PRG4-deficient OA SF was significantly diminished as compared to normal (mean ± SEM <μ(kinetic, Neq) > = 0.043 ± 0.008 versus 0.025 ± 0.002; P < 0.05) and was restored when supplemented with PRG4 (<μ(kinetic, Neq) > = 0.023 ± 0.003; P < 0.05).
  
  
  CONCLUSIONS
  These results indicate that some OA SF may have decreased PRG4 levels and diminished cartilage boundary-lubricating ability as compared to normal SF and that PRG4 supplementation can restore normal cartilage boundary lubrication function to these OA SF.
authors.affiliation: University of Calgary, Calgary, Alberta, Canada.
authors.forename: Taryn E
authors.initials: TE
authors.lastname: Ludwig
authors.forename: Jenelle R
authors.initials: JR
authors.lastname: McAllister
authors.forename: Victor
authors.initials: V
authors.lastname: Lun
authors.forename: J Preston
authors.initials: JP
authors.lastname: Wiley
authors.forename: Tannin A
authors.initials: TA
authors.lastname: Schmidt
mesh_terms: D000368:Aged; D002358:Cartilage, Articular / Q000378:metabolism / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D017276:Friction; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D007719:Knee Joint / Q000378:metabolism / Q000503:physiopathology*; D008153:Lubrication; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D020370:Osteoarthritis, Knee / Q000378:metabolism / Q000503:physiopathology*; D011509:Proteoglycans / Q000172:deficiency* / Q000378:metabolism / Q000494:pharmacology*; D013582:Synovial Fluid / Q000187:drug effects* / Q000502:physiology*; D000099158:Proteoglycan 4
chemical_list: D006820:Hyaluronic Acid; D011509:Proteoglycans; C419197:PRG4 protein, human; D000099158:Proteoglycan 4