PMID- 9876398
OWN - NLM
STAT- MEDLINE
DCOM- 19990125
LR  - 20161018
IS  - 1063-4584 (Print)
IS  - 1063-4584 (Linking)
VI  - 6
IP  - 4
DP  - 1998 Jul
TI  - Increased secretion and activity of matrix metalloproteinase-3 in synovial 
      tissues and chondrocytes from experimental osteoarthritis.
PG  - 286-94
AB  - OBJECTIVE: The aim of this study was to define the relative regulation of matrix 
      metalloproteinase-3 (MMP-3), and tissue inhibitor of metalloproteinases-1 
      (TIMP-1), in chondrocytes and synovium in experimental osteoarthritis (EOA). 
      METHODS: Partial-meniscectomized (PM) rabbits, surgical sham controls (SH), and 
      normal non-surgical controls (N) were killed at times corresponding to early 
      degenerative lesions (4 weeks) and increasingly progressive stages of EOA at 8 
      and 12 weeks post-PM. MMP-3 activity was measured in conditioned media from 
      chondrocytes and synovium using a peptide cleavage assay with substance P (SP) as 
      the substrate. TIMP-1 was quantitated using an enzyme-linked immunosorbent assay 
      (ELISA). RESULTS: Early degenerative lesions (4 weeks post-PM) were characterized 
      by inflammatory responses in the synovium accompanied by a significant rise of 
      MMP-3 activity in synovial cultures (P < 0.05). At 8 weeks there was no 
      discernible inflammation, and MMP-3 activity in EOA synovial cultures was 
      comparable to that in the controls; this was followed by a second increase in 
      MMP-3 activity in EOA samples at 12 weeks. MMP-3 activity was significantly 
      elevated in EOA chondrocyte cultures at 8 weeks post-PM relative to N controls, 
      corresponding to the most destructive phase of EOA, but not in the early phase (4 
      weeks) or 'late' degenerative phase (12 weeks). Medium derived from chondrocytes 
      contained little or no TIMP-1. Synovia secreted relatively higher amounts of 
      TIMP-1, and this was elevated at 8 weeks post-PM relative to the SH controls. The 
      majority (approximately 90%) of MMP-3 activity could be inhibited using 
      recombinant TIMP-1 or a hydroxamate MMP inhibitor. Complete inhibition was 
      achieved with EDTA or 1,10 phenanthroline. CONCLUSION: Together, these data 
      indicate that in EOA, MMP-3 is initially upregulated in the synovium which may 
      play a pivotal role in the pathogenesis of cartilage lesions. In contrast, 
      chondrocyte-derived MMP-3 is upregulated in the later phases of EOA, contributing 
      further to progression of cartilage lesions.
FAU - Mehraban, F
AU  - Mehraban F
AD  - Case Western Reserve University, Department of Medicine, Cleveland, Ohio 
      44106-4946, USA. fxm5@po.cwru.edu
FAU - Lark, M W
AU  - Lark MW
FAU - Ahmed, F N
AU  - Ahmed FN
FAU - Xu, F
AU  - Xu F
FAU - Moskowitz, R W
AU  - Moskowitz RW
LA  - eng
GR  - 26108/PHS HHS/United States
GR  - 30134/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Osteoarthritis Cartilage
JT  - Osteoarthritis and cartilage
JID - 9305697
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Animals
MH  - Chondrocytes/*enzymology
MH  - Chromatography, High Pressure Liquid
MH  - Culture Media, Conditioned
MH  - Culture Techniques
MH  - Female
MH  - Matrix Metalloproteinase 3/*metabolism
MH  - Osteoarthritis, Knee/*enzymology/pathology
MH  - Rabbits
MH  - Synovial Membrane/*enzymology/pathology
MH  - Tissue Inhibitor of Metalloproteinase-1/metabolism
EDAT- 1999/01/07 00:00
MHDA- 1999/01/07 00:01
CRDT- 1999/01/07 00:00
PHST- 1999/01/07 00:00 [pubmed]
PHST- 1999/01/07 00:01 [medline]
PHST- 1999/01/07 00:00 [entrez]
AID - S1063-4584(98)90122-4 [pii]
AID - 10.1053/joca.1998.0122 [doi]
PST - ppublish
SO  - Osteoarthritis Cartilage. 1998 Jul;6(4):286-94. doi: 10.1053/joca.1998.0122.