PMID- 17195217
OWN - NLM
STAT- MEDLINE
DCOM- 20070215
LR  - 20131121
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 56
IP  - 1
DP  - 2007 Jan
TI  - Crucial role of macrophages in matrix metalloproteinase-mediated cartilage 
      destruction during experimental osteoarthritis: involvement of matrix 
      metalloproteinase 3.
PG  - 147-57
AB  - OBJECTIVE: To explore the involvement of synovial macrophages in early cartilage 
      damage in osteoarthritis (OA), and to identify the role of matrix 
      metalloproteinase 3 (MMP-3) in the pathology of early and late OA. METHODS: The 
      role of synovial macrophages in MMP-mediated damage in OA was studied by 
      depleting synovial macrophages prior to elicitation of a collagenase-induced 
      instability model of OA. The expression of MMP in synovium and cartilage was 
      monitored using TaqMan analysis. In spontaneous and induced OA, cartilage 
      pathology was scored in MMP-3-knockout mice and control mice, by histologic 
      assessment and VDIPEN staining. RESULTS: On day 14 following induction of OA, 
      MMP-mediated neoepitopes were detected in cartilage from mice with mild 
      experimental OA (mean +/- SD positively stained surface area 20 +/- 3.2%). 
      Remarkably, by depleting synovial macrophages prior to induction of OA, the 
      generation of MMP-induced neoepitopes was largely prevented (mean +/- SD 
      positively stained surface area 5 +/- 1%; P< 0.001), indicating an important role 
      for synovial macrophages in the occurrence of MMP-mediated cartilage damage. We 
      observed a strong decrease in MMP-3 and MMP-9 expression in synovial but not 
      cartilage tissue in macrophage-depleted joints. Among 2-year-old mice, 
      spontaneous OA-like changes in the lining layer were significantly decreased in 
      MMP-3-knockout mice compared with control mice. Even more striking was the 67% 
      reduction in the occurrence of severe cartilage damage in MMP-3-knockout mice. In 
      addition, MMP-mediated VDIPEN expression was significantly decreased, indicating 
      reduced MMP-mediated cartilage breakdown. CONCLUSION: The results of this study 
      prove that MMP-3 is involved in the generation of severe cartilage damage in 
      murine OA. Synovial macrophages are crucial in early MMP activity and appear to 
      mediate MMP production in synovium rather than cartilage.
FAU - Blom, Arjen B
AU  - Blom AB
AD  - Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands. 
      a.blom@reuma.umcn.nl
FAU - van Lent, Peter L
AU  - van Lent PL
FAU - Libregts, Sten
AU  - Libregts S
FAU - Holthuysen, Astrid E
AU  - Holthuysen AE
FAU - van der Kraan, Peter M
AU  - van der Kraan PM
FAU - van Rooijen, Nico
AU  - van Rooijen N
FAU - van den Berg, Wim B
AU  - van den Berg WB
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Bone Density Conservation Agents)
RN  - 0 (Oligopeptides)
RN  - 0 (Peptide Fragments)
RN  - 0 (peptide VDIPEN)
RN  - 0813BZ6866 (Clodronic Acid)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Animals
MH  - Arthritis, Experimental/*enzymology/pathology
MH  - Bone Density Conservation Agents/pharmacology
MH  - Cartilage, Articular/*enzymology/pathology
MH  - Clodronic Acid/pharmacology
MH  - Immunoenzyme Techniques
MH  - Macrophages/drug effects/*enzymology/pathology
MH  - Matrix Metalloproteinase 3/genetics/*metabolism
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Oligopeptides/metabolism
MH  - Osteoarthritis, Knee/*enzymology/pathology
MH  - Peptide Fragments/metabolism
MH  - Synovial Membrane/drug effects/pathology
EDAT- 2006/12/30 09:00
MHDA- 2007/02/16 09:00
CRDT- 2006/12/30 09:00
PHST- 2006/12/30 09:00 [pubmed]
PHST- 2007/02/16 09:00 [medline]
PHST- 2006/12/30 09:00 [entrez]
AID - 10.1002/art.22337 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2007 Jan;56(1):147-57. doi: 10.1002/art.22337.