PMID- 16087381
OWN - NLM
STAT- MEDLINE
DCOM- 20060613
LR  - 20200205
IS  - 1297-319X (Print)
IS  - 1297-319X (Linking)
VI  - 73
IP  - 1
DP  - 2006 Jan
TI  - Cartilage breakdown in rheumatoid arthritis.
PG  - 29-36
AB  - Rheumatoid arthritis (RA) is a connective tissue disease characterized by 
      destruction of the joint cartilage and subsequently of the underlying bone. 
      Cartilage destruction is due to proteolysis by enzymes called metalloproteinases 
      (MMPs), whose production and expression are regulated by numerous local mediators 
      such as cytokines, growth factors, prostaglandins, oxygen species, and 
      neuropeptides. MMP activation is largely due to a stimulatory effect of cytokines 
      including IL-1beta and TNFalpha. When these cytokines bind to their membrane 
      receptor, they set off signaling cascades, with activation of TGFbeta-activating 
      kinase (TAK-1), of NF-kappaB by Ikappa-B kinase, of mitogen-activated protein 
      kinases (MAP kinases), and finally of activator protein-1 (AP-1). Tissue 
      inhibitors of MMPs (TIMPs) specifically inhibit MMPs. The interrelations between 
      joint inflammation and joint destruction remain poorly understood. Experimental 
      data suggest that IL-1 may be involved chiefly in joint destruction and TNF in 
      joint inflammation. However, TNF antagonists are potent inhibitors of joint 
      destruction in clinical practice. These results suggest that the mediators 
      function as a network and that inhibition of a single mediator can affect the 
      entire web. Insights gained into the innermost mechanisms of cartilage breakdown 
      in patients with RA have led to major therapeutic breakthroughs. Thus, TNF 
      antagonists have proved highly effective in RA. Future progress will no doubt 
      stem from new knowledge about the extracellular mediators and intracellular 
      signaling pathways that lead to the production and activation of enzymes 
      responsible for cartilage degradation.
FAU - Rannou, Francois
AU  - Rannou F
AD  - Research Unit UMR-S 530-Inserm-Paris 5 University, France.
FAU - Francois, Mathias
AU  - Francois M
FAU - Corvol, Marie-Therese
AU  - Corvol MT
FAU - Berenbaum, Francis
AU  - Berenbaum F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20050706
PL  - France
TA  - Joint Bone Spine
JT  - Joint bone spine
JID - 100938016
RN  - 0 (Biomarkers)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - EC 3.4.- (Metalloproteases)
SB  - IM
MH  - Animals
MH  - Arthritis, Rheumatoid/enzymology/*pathology
MH  - Biomarkers/metabolism
MH  - Cartilage, Articular/*enzymology/pathology
MH  - Humans
MH  - Metalloproteases/*metabolism
MH  - Tissue Inhibitor of Metalloproteinases/metabolism
RF  - 82
EDAT- 2005/08/10 09:00
MHDA- 2006/06/14 09:00
CRDT- 2005/08/10 09:00
PHST- 2004/12/12 00:00 [received]
PHST- 2004/12/27 00:00 [accepted]
PHST- 2005/08/10 09:00 [pubmed]
PHST- 2006/06/14 09:00 [medline]
PHST- 2005/08/10 09:00 [entrez]
AID - S1297-319X(05)00095-3 [pii]
AID - 10.1016/j.jbspin.2004.12.013 [doi]
PST - ppublish
SO  - Joint Bone Spine. 2006 Jan;73(1):29-36. doi: 10.1016/j.jbspin.2004.12.013. Epub 
      2005 Jul 6.