PMID- 8895151
OWN - NLM
STAT- MEDLINE
DCOM- 19970603
LR  - 20131121
IS  - 0315-162X (Print)
IS  - 0315-162X (Linking)
VI  - 23
IP  - 10
DP  - 1996 Oct
TI  - Effects of indomethacin on the production of matrix metalloproteinase-3 and 
      tissue inhibitor of metalloproteinases-1 by human articular chondrocytes.
PG  - 1739-43
AB  - OBJECTIVE: To study the action of indomethacin on cartilage catabolic activity by 
      comparing the production of a matrix degrading proteinase and its inhibitor in 
      human articular chondrocyte cultures. METHODS: Matrix metalloproteinase-3 (MMP-3) 
      and tissue inhibitor of metalloproteinases-1 (TIMP-1) in conditioned medium from 
      human articular chondrocyte cultures were measured using a one-step sandwich 
      enzyme immunoassay. TIMP-1 mRNA expression was analyzed by Northern blotting 
      using a 0.6 kb cDNA probe for human TIMP-1. RESULTS: Human recombinant 
      interleukin 1 beta (IL-1 beta) increased MMP-3 levels in primary chondrocyte 
      cultures. Indomethacin at 10(-5) M inhibited this IL-1 beta stimulation, but had 
      no effect in the therapeutic range (10(-6)-10(-7) M). Low levels of indomethacin 
      (10(-7) M) significantly increased the production of TIMP-1 by chondrocytes. 
      Synthesis of TIMP-1 appeared to be inhibited by prostaglandin E2 (PGE2), since 
      exogenously added PGE2 reversed the stimulating effect of indomethacin on TIMP-1 
      production. Northern blot analysis showed that 10(-7) M indomethacin increased 
      TIMP-1 mRNA levels in chondrocytes. CONCLUSION: Our findings indicate that low 
      levels of indomethacin can benefit matrix metabolism by affecting the balance of 
      proteinases to their inhibitors in human articular cartilage.
FAU - Yamada, H
AU  - Yamada H
AD  - Department of Orthopaedic Surgery, National Defense Medical College, Saitama, 
      Japan.
FAU - Kikuchi, T
AU  - Kikuchi T
FAU - Nemoto, O
AU  - Nemoto O
FAU - Obata, K
AU  - Obata K
FAU - Sato, H
AU  - Sato H
FAU - Seiki, M
AU  - Seiki M
FAU - Shinmei, M
AU  - Shinmei M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Canada
TA  - J Rheumatol
JT  - The Journal of rheumatology
JID - 7501984
RN  - 0 (Glycoproteins)
RN  - 0 (Interleukin-1)
RN  - 0 (Matrix Metalloproteinase Inhibitors)
RN  - 0 (Protease Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - EC 3.4.24.- (Collagenases)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - K7Q1JQR04M (Dinoprostone)
RN  - XXE1CET956 (Indomethacin)
SB  - IM
MH  - Blotting, Northern
MH  - Cartilage, Articular/cytology/drug effects/*metabolism
MH  - Cells, Cultured
MH  - Collagenases/*metabolism
MH  - Dinoprostone/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Glycoproteins/genetics/*metabolism
MH  - Humans
MH  - Indomethacin/*pharmacology
MH  - Interleukin-1/pharmacology
MH  - Matrix Metalloproteinase 3/*metabolism
MH  - Matrix Metalloproteinase Inhibitors
MH  - Protease Inhibitors/*metabolism
MH  - RNA, Messenger/analysis
MH  - Tissue Inhibitor of Metalloproteinases
EDAT- 1996/10/01 00:00
MHDA- 1996/10/01 00:01
CRDT- 1996/10/01 00:00
PHST- 1996/10/01 00:00 [pubmed]
PHST- 1996/10/01 00:01 [medline]
PHST- 1996/10/01 00:00 [entrez]
PST - ppublish
SO  - J Rheumatol. 1996 Oct;23(10):1739-43.