title: Association between synovial fluid levels of aggrecan ARGS fragments and radiographic progression in knee osteoarthritis.
abstract: BACKGROUND
  Aggrecanase cleavage at the (392)Glu-(393)Ala bond in the interglobular domain (IGD) of aggrecan, releasing N-terminal (393)ARGS fragments, is an early key event in arthritis and joint injuries. We determined whether synovial fluid (SF) levels of ARGS-aggrecan distinguish subjects with progressive radiographic knee osteoarthritis (ROA) from those with stable or no ROA.
  
  
  METHODS
  We studied 141 subjects who, at examination A, had been given meniscectomies an average of 18 years earlier (range, 15 to 22 years). Seventeen individuals without surgery, and without known injury to the menisci or cruciate ligaments, were used as references. At examinations A and B, with a mean follow-up time of 7.5 years, we obtained SF and standing tibiofemoral and skyline patellofemoral radiographs. SF ARGS-aggrecan was measured with an electrochemiluminescence immunoassay, and we graded radiographs according to the OARSI atlas. The association between SF ARGS levels at examination A and progression of radiographic features of knee OA between examinations A and B was assessed by using logistic regression adjusted for age, gender, body mass index, and time between examinations, and stratified by ROA status at examination A.
  
  
  RESULTS
  We found a weak negative association between SF ARGS concentrations and loss of joint space: the likelihood of progression of radiographic joint space narrowing decreased 0.9 times per picomole per milliliter increase in ARGS (odds ratio (OR) 0.89; 95% confidence interval (CI), 0.79 to 0.996). In subjects with and without preexisting ROA at examination A, the association was OR, 0.96; 0.81 to 1.13; and 0.77; 0.62 to 0.95, respectively. Average levels of SF ARGS 18 years after meniscectomy were no different from those of reference subjects and were not correlated to radiographic status at examination A.
  
  
  CONCLUSIONS
  In subjects with previous knee meniscectomy but without ROA, levels of SF ARGS-aggrecan were weakly and inversely associated with increased loss of joint space over a period of 7.5 years.
authors.affiliation: Department of Orthopedics, Clinical Sciences Lund, Lund University, BMC C12, Klinikgatan 28, SE-221 84 Lund, Sweden. staffan.larsson@med.lu.se
authors.forename: Staffan
authors.initials: S
authors.lastname: Larsson
authors.forename: Martin
authors.initials: M
authors.lastname: Englund
authors.forename: André
authors.initials: A
authors.lastname: Struglics
authors.forename: L Stefan
authors.initials: LS
authors.lastname: Lohmander
mesh_terms: D000328:Adult; D000368:Aged; D053674:Aggrecans / Q000032:analysis*; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western; D018450:Disease Progression; D005260:Female; D006801:Humans; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging* / Q000378:metabolism*; D010446:Peptide Fragments / Q000032:analysis; D011859:Radiography; D013582:Synovial Fluid / Q000737:chemistry
chemical_list: D053674:Aggrecans; D015415:Biomarkers; D010446:Peptide Fragments