PMID- 22824140
OWN - NLM
STAT- MEDLINE
DCOM- 20130612
LR  - 20211021
IS  - 1471-2474 (Electronic)
IS  - 1471-2474 (Linking)
VI  - 13
DP  - 2012 Jul 23
TI  - Matrix metalloproteinase protein expression profiles cannot distinguish between 
      normal and early osteoarthritic synovial fluid.
PG  - 126
LID - 10.1186/1471-2474-13-126 [doi]
AB  - BACKGROUND: Osteoarthritis (OA) and rheumatoid arthritis (RA) are diseases which 
      result in the degeneration of the joint surface articular cartilage. Matrix 
      metalloproteinases (MMPs) are enzymes that aid in the natural remodelling of 
      tissues throughout the body including cartilage. However, some MMPs have been 
      implicated in the progression of OA and RA as their expression levels and 
      activation states can change dramatically with the onset of disease. Yet, it 
      remains unknown if normal and arthritic joints demonstrate unique MMPs expression 
      profiles, and if so, can the MMP expression profile be used to identify patients 
      with early OA. In this study, the synovial fluid protein expression levels for 
      MMPs 1, 2, 3, 7, 8, 9, 12 & 13, as well as those for the Tissue Inhibitors of 
      MMPs (TIMPs) 1, 2, 3, & 4 were examined in highly characterized normal knee 
      joints, and knee joints with clinically diagnosed OA (early and advanced) or RA. 
      The purpose of this study was to determine if normal, OA, and RA patients exhibit 
      unique expression profiles for a sub-set of MMPs, and if early OA patients have a 
      unique MMP expression profile that could be used as an early diagnostic marker. 
      METHODS: Synovial fluid was aspirated from stringently characterized normal knee 
      joints, and in joints diagnosed with either OA (early and advanced) or RA. 
      Multiplexing technology was employed to quantify protein expression levels for 8 
      MMPs and 4 TIMPs in the synovial fluid of 12 patients with early OA, 17 patients 
      diagnosed with advanced OA, 15 with RA and 25 normal knee joints. Principle 
      component analysis (PCA) was used to reveal which MMPs were most influential in 
      the distinction between treatment groups. K - means clustering was used to verify 
      the visual grouping of subjects via PCA. RESULTS: Significant differences in the 
      expression levels of MMPs and TIMPs were observed between normal and arthritic 
      synovial fluids (with the exception of MMP 12). PCA demonstrated that MMPs 2, 8 & 
      9 can be used to effectively separate individuals diagnosed with advanced 
      arthritis from early osteoarthritic and normal individuals, however, these MMP 
      profiles do not separate early OA from normal synovial fluid. An apparent 
      separation between advanced OA and RA subjects was also revealed through PCA. 
      K-means clustering verified the presence of 3 clusters: normal joints clustered 
      with early OA, and separate clusters of advanced OA or RA. CONCLUSIONS: This 
      study demonstrates that unique MMP and TIMP expression profiles are present 
      within normal, advanced OA and RA synovial fluid. These MMP profiles can be used 
      to distinguish advanced OA & RA synovial fluid from early OA & normal synovial 
      fluid, and even between synovial fluid samples from OA and RA joints. Although 
      this methodology cannot be used for the diagnosis of early OA, high throughput 
      multiplex technology of MMPs and TIMPs in synovial fluid may prove useful in 
      determining the severity of the disease state, and/or quantifying the response of 
      individuals to disease interventions.
FAU - Heard, Bryan J
AU  - Heard BJ
AD  - Faculty of Medicine, University of Calgary, Calgary, AB, Canada.
FAU - Martin, Liam
AU  - Martin L
FAU - Rattner, Jerome B
AU  - Rattner JB
FAU - Frank, Cyril B
AU  - Frank CB
FAU - Hart, David A
AU  - Hart DA
FAU - Krawetz, Roman
AU  - Krawetz R
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120723
PL  - England
TA  - BMC Musculoskelet Disord
JT  - BMC musculoskeletal disorders
JID - 100968565
RN  - 0 (Biomarkers)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Arthritis, Rheumatoid/*diagnosis/enzymology
MH  - Biomarkers/analysis
MH  - Case-Control Studies
MH  - Cluster Analysis
MH  - Early Diagnosis
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Humans
MH  - Male
MH  - Matrix Metalloproteinases/*analysis
MH  - Middle Aged
MH  - Multivariate Analysis
MH  - Osteoarthritis, Knee/*diagnosis/enzymology
MH  - Predictive Value of Tests
MH  - Principal Component Analysis
MH  - Synovial Fluid/*enzymology
MH  - Tissue Inhibitor of Metalloproteinases/analysis
PMC - PMC3532375
EDAT- 2012/07/25 06:00
MHDA- 2013/06/13 06:00
PMCR- 2012/07/23
CRDT- 2012/07/25 06:00
PHST- 2011/12/06 00:00 [received]
PHST- 2012/07/02 00:00 [accepted]
PHST- 2012/07/25 06:00 [entrez]
PHST- 2012/07/25 06:00 [pubmed]
PHST- 2013/06/13 06:00 [medline]
PHST- 2012/07/23 00:00 [pmc-release]
AID - 1471-2474-13-126 [pii]
AID - 10.1186/1471-2474-13-126 [doi]
PST - epublish
SO  - BMC Musculoskelet Disord. 2012 Jul 23;13:126. doi: 10.1186/1471-2474-13-126.