PMID- 26991527
OWN - NLM
STAT- MEDLINE
DCOM- 20170707
LR  - 20181113
IS  - 2326-5205 (Electronic)
IS  - 2326-5191 (Print)
IS  - 2326-5191 (Linking)
VI  - 68
IP  - 9
DP  - 2016 Sep
TI  - Acute Molecular Changes in Synovial Fluid Following Human Knee Injury: 
      Association With Early Clinical Outcomes.
PG  - 2129-40
LID - 10.1002/art.39677 [doi]
AB  - OBJECTIVE: To investigate whether molecules found to be up-regulated within hours 
      of surgical joint destabilization in the mouse are also elevated in the analogous 
      human setting of acute knee injury, how this molecular response varies between 
      individuals, and whether it is related to patient-reported outcomes in the 3 
      months after injury. METHODS: Seven candidate molecules were analyzed in blood 
      and synovial fluid (SF) from 150 participants with recent structural knee injury 
      at baseline (<8 weeks from injury) and in blood at 14 days and 3 months following 
      baseline. Knee Injury and Osteoarthritis Outcome Score 4 (KOOS4 ) was obtained at 
      baseline and 3 months. Patient and control samples were compared using Meso Scale 
      Discovery platform assays or enzyme-linked immunosorbent assay. RESULTS: Six of 
      the 7 molecules were significantly elevated in human SF immediately after injury: 
      interleukin-6 (IL-6), monocyte chemotactic protein 1, matrix metalloproteinase 3 
      (MMP-3), tissue inhibitor of metalloproteinases 1 (TIMP-1), activin A, and tumor 
      necrosis factor-stimulated gene 6 (TSG-6). There was low-to-moderate correlation 
      with blood measurements. Three of the 6 molecules were significantly associated 
      with baseline KOOS4 (those with higher SF IL-6, TIMP-1, or TSG-6 had lower KOOS4 
      ). These 3 molecules, MMP-3, and activin A were all significantly associated with 
      greater improvement in KOOS4 over 3 months, after adjustment for other relevant 
      factors. Of these, IL-6 alone significantly accounted for the molecular 
      contribution to baseline KOOS4 and change in KOOS4 over 3 months. CONCLUSION: Our 
      findings validate relevant human biomarkers of tissue injury identified in a 
      mouse model. Analysis of SF rather than blood more accurately reflects this 
      response. The response is associated with patient-reported outcomes over this 
      early period, with SF IL-6 acting as a single representative marker. Longitudinal 
      outcomes will determine if these molecules are biomarkers of subsequent disease 
      risk.
CI  - (c) 2016 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. 
      on behalf of the American College of Rheumatology.
FAU - Watt, Fiona E
AU  - Watt FE
AD  - Arthritis Research UK Centre for Osteoarthritis Pathogenesis, Kennedy Institute 
      of Rheumatology, University of Oxford, Oxford, UK.
FAU - Paterson, Erin
AU  - Paterson E
AD  - Arthritis Research UK Centre for Osteoarthritis Pathogenesis, Kennedy Institute 
      of Rheumatology, University of Oxford, Oxford, UK.
FAU - Freidin, Andrew
AU  - Freidin A
AD  - Arthritis Research UK Centre for Osteoarthritis Pathogenesis, Kennedy Institute 
      of Rheumatology, University of Oxford, Oxford, UK.
FAU - Kenny, Mark
AU  - Kenny M
AD  - Fortius Clinic, Imperial College Healthcare NHS Trust, St. Mary's Hospital, 
      London, UK.
FAU - Judge, Andrew
AU  - Judge A
AD  - NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK, 
      and University of Southampton, Southampton, UK.
FAU - Saklatvala, Jeremy
AU  - Saklatvala J
AD  - Arthritis Research UK Centre for Osteoarthritis Pathogenesis, Kennedy Institute 
      of Rheumatology, University of Oxford, Oxford, UK.
FAU - Williams, Andy
AU  - Williams A
AD  - Arthritis Research UK Centre for Osteoarthritis Pathogenesis, Kennedy Institute 
      of Rheumatology, University of Oxford, Oxford, UK, and Fortius Clinic, London, 
      UK.
FAU - Vincent, Tonia L
AU  - Vincent TL
AD  - Arthritis Research UK Centre for Osteoarthritis Pathogenesis, Kennedy Institute 
      of Rheumatology, University of Oxford, Oxford, UK.
LA  - eng
GR  - 20205/Arthritis Research UK/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheumatol
JT  - Arthritis & rheumatology (Hoboken, N.J.)
JID - 101623795
RN  - 0 (Biomarkers)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Animals
MH  - Biomarkers/analysis
MH  - Female
MH  - Humans
MH  - Knee Injuries/*blood/surgery
MH  - Male
MH  - Mice
MH  - Middle Aged
MH  - Synovial Fluid/*chemistry
MH  - Time Factors
MH  - Treatment Outcome
MH  - Young Adult
PMC - PMC5006850
EDAT- 2016/03/19 06:00
MHDA- 2017/07/08 06:00
PMCR- 2016/08/31
CRDT- 2016/03/19 06:00
PHST- 2015/09/23 00:00 [received]
PHST- 2016/03/03 00:00 [accepted]
PHST- 2016/03/19 06:00 [entrez]
PHST- 2016/03/19 06:00 [pubmed]
PHST- 2017/07/08 06:00 [medline]
PHST- 2016/08/31 00:00 [pmc-release]
AID - ART39677 [pii]
AID - 10.1002/art.39677 [doi]
PST - ppublish
SO  - Arthritis Rheumatol. 2016 Sep;68(9):2129-40. doi: 10.1002/art.39677.