PMID- 19909233
OWN - NLM
STAT- MEDLINE
DCOM- 20100916
LR  - 20190911
IS  - 1873-5592 (Electronic)
IS  - 1389-4501 (Linking)
VI  - 10
IP  - 12
DP  - 2009 Dec
TI  - Targeting matrix metalloproteinases in inflammatory conditions.
PG  - 1245-54
AB  - The matrix metalloproteinases (MMPs) and their endogenous regulators, the tissue 
      inhibitors of MMPs (TIMPs) are responsible for the physiological remodelling of 
      the extracellular matrix (ECM) in healthy connective tissues. MMPs are also 
      involved in the regulation of cell behaviour via the release of growth factors 
      and cytokines from the substrates they cleave, increasing the magnitude of their 
      effects. Excess MMP activity is associated with ECM destruction in various 
      inflammatory conditions, such as osteoarthritis (OA), while MMP under-activity 
      potentially impairs healing by promoting fibrosis and preventing the effective 
      removal of scar tissue. Both direct (TIMPs, small molecule MMP inhibitor drugs, 
      blocking antibodies and anti-sense technologies) and indirect (glucocorticoids 
      and non-steroidal anti-inflammatory drugs, statins, anti-sense technologies and 
      various phytochemicals) strategies for MMP inhibition have been proposed and 
      investigated. The strategy of MMP inhibition for degenerative and neoplastic 
      diseases has been relatively unsuccessful due to undesired sequelae, often caused 
      by non-selectivity of the MMP inhibition method. Therapeutic strategies for 
      MMP-related conditions ideally should regulate MMP activity in order to maintain 
      the optimum balance between MMPs and TIMPs. By avoiding complete inhibition it 
      may be possible to prevent the complications of MMP over- and under-activity. 
      Furthermore, MMP sub-type specificity is critical for minimising detrimental 
      off-target effects that have been observed with broad-spectrum MMP inhibitors. 
      Any potential MMP inhibitor or modulator must be subjected to rigorous 
      pharmacokinetic, toxicity and safety studies and data obtained using in vitro 
      models must be verified in clinically relevant animal models before therapeutic 
      use is considered.
FAU - Clutterbuck, A L
AU  - Clutterbuck AL
AD  - University of Nottingham, Leicestershire, UK.
FAU - Asplin, K E
AU  - Asplin KE
FAU - Harris, P
AU  - Harris P
FAU - Allaway, D
AU  - Allaway D
FAU - Mobasheri, A
AU  - Mobasheri A
LA  - eng
GR  - BBS/S/M/2006/13141/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United Arab Emirates
TA  - Curr Drug Targets
JT  - Current drug targets
JID - 100960531
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Antibodies, Blocking)
RN  - 0 (Matrix Metalloproteinase Inhibitors)
RN  - 0 (Protease Inhibitors)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/*therapeutic use
MH  - Antibodies, Blocking/therapeutic use
MH  - Humans
MH  - Inflammation/*drug therapy
MH  - *Matrix Metalloproteinase Inhibitors
MH  - Protease Inhibitors/*therapeutic use
MH  - Tissue Inhibitor of Metalloproteinases/therapeutic use
RF  - 142
EDAT- 2009/11/17 06:00
MHDA- 2010/09/18 06:00
CRDT- 2009/11/14 06:00
PHST- 2009/04/17 00:00 [received]
PHST- 2009/09/01 00:00 [accepted]
PHST- 2009/11/14 06:00 [entrez]
PHST- 2009/11/17 06:00 [pubmed]
PHST- 2010/09/18 06:00 [medline]
AID - CDT-ms35 [pii]
AID - 10.2174/138945009789753264 [doi]
PST - ppublish
SO  - Curr Drug Targets. 2009 Dec;10(12):1245-54. doi: 10.2174/138945009789753264.