title: ADAMTS-4 activity in synovial fluid as a biomarker of inflammation and effusion.
abstract: OBJECTIVE
  To evaluate the potential of ADAMTS-4 (aggrecanase -1) activity in synovial fluid (SF) as a biomarker of knee injury and joint disease.
  
  
  METHODS
  We have measured ADAMTS-4 activity in the synovial fluid of 170 orthopaedic patients with different degrees of joint pathology, using a commercial ADAMTS-4 fluorescence resonance energy transfer (FRET) substrate assay. Patients were classified at arthroscopy as (i) macroscopically normal, (ii) with an injury of the meniscus, anterior cruciate ligament or chondral/osteochondral defects or (iii) with osteoarthritis, and the influence of independent factors (age, patient group, effusion and synovial inflammation) on ADAMTS-4 activity levels was assessed.
  
  
  RESULTS
  In most patients (106/170) ADAMTS-4 activity was undetectable; ADAMTS-4 ranged from 0 to 2.8 ng/mL in synovial fluid from patients with an injury, 0-4.1 ng/mL in osteoarthritic patients and 4.0-12.3 ng/mL in patients with large effusions. Four independent variables each significantly influenced ADAMTS-4 activity in synovial fluid (all P < 0.001): age (concordance = 0.69), presence of osteoarthritis (OA) (concordance = 0.66), level of effusion (concordance = 0.78) and inflammation (concordance = 0.68). Not only did effusion influence the amount of ADAMTS-4 activity most strongly, but it also did this in an ordered manner (P < 0.001).
  
  
  CONCLUSIONS
  The main finding of this study is that ADAMTS-4 levels in synovial fluid are most strongly correlated with inflammation and severity of effusion in the knee. Further study is required to determine if it could provide a useful tool to aid clinical diagnoses, indicate treatment, to monitor progression of joint degeneration or OA or alternatively the success of treatment.
authors.affiliation: Robert Jones & Agnes Hunt Orthopaedic Hospital NHS Foundation Trust, Oswestry, Shropshire, UK; Keele University, Keele, Staffordshire, UK. Electronic address: sally.roberts@rjah.nhs.uk.
authors.forename: S
authors.initials: S
authors.lastname: Roberts
authors.affiliation: Robert Jones & Agnes Hunt Orthopaedic Hospital NHS Foundation Trust, Oswestry, Shropshire, UK. Electronic address: helena.evans@rjah.nhs.uk.
authors.forename: H
authors.initials: H
authors.lastname: Evans
authors.affiliation: Robert Jones & Agnes Hunt Orthopaedic Hospital NHS Foundation Trust, Oswestry, Shropshire, UK; Keele University, Keele, Staffordshire, UK. Electronic address: karina.wright@rjah.nhs.uk.
authors.forename: K
authors.initials: K
authors.lastname: Wright
authors.affiliation: Northallerton Hospital, Yorkshire, UK. Electronic address: shelly.cameron@stees.nhs.uk.
authors.forename: L
authors.initials: L
authors.lastname: van Niekerk
authors.affiliation: School of Bioscience, Cardiff University, UK. Electronic address: caterson@cardiff.ac.uk.
authors.forename: B
authors.initials: B
authors.lastname: Caterson
authors.affiliation: Robert Jones & Agnes Hunt Orthopaedic Hospital NHS Foundation Trust, Oswestry, Shropshire, UK; Keele University, Keele, Staffordshire, UK. Electronic address: james.richardson@nhs.net.
authors.forename: J B
authors.initials: JB
authors.lastname: Richardson
authors.affiliation: Robert Jones & Agnes Hunt Orthopaedic Hospital NHS Foundation Trust, Oswestry, Shropshire, UK. Electronic address: drkhskumar@yahoo.com.
authors.forename: K H S
authors.initials: KH
authors.lastname: Kumar
authors.affiliation: Robert Jones & Agnes Hunt Orthopaedic Hospital NHS Foundation Trust, Oswestry, Shropshire, UK; Keele University, Keele, Staffordshire, UK. Electronic address: jan.kuiper@nhs.net.
authors.forename: J H
authors.initials: JH
authors.lastname: Kuiper
mesh_terms: D051722:ADAM Proteins / Q000032:analysis*; D000071121:ADAMTS4 Protein; D000328:Adult; D015415:Biomarkers / Q000032:analysis; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D007592:Joint Diseases / Q000201:enzymology*; D007718:Knee Injuries / Q000201:enzymology*; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000201:enzymology*; D011348:Procollagen N-Endopeptidase / Q000032:analysis*; D013582:Synovial Fluid / Q000737:chemistry*
chemical_list: D015415:Biomarkers; D051722:ADAM Proteins; D011348:Procollagen N-Endopeptidase; D000071121:ADAMTS4 Protein; C000603918:ADAMTS4 protein, human
keywords: ADAMTS-4 activity; Effusion; Inflammation; Knee osteoarthritis; Synovial fluid