Low molecular weight inhibitors of matrix metalloproteinases can enhance the expression of matrix metalloproteinase-2 (gelatinase A) without inhibiting its activation.
BACKGROUND
In the current study, the authors investigated the effects of synthetic low molecular weight inhibitors of matrix metalloproteinases (MMPs) on the expression and activation of MMP-2 in a three-dimensional tissue system.


METHODS
Rabbit periosteal explants were cultured with or without various concentrations of the MMP inhibitors CT1166, CT1399, or CT1746, and conditioned media and tissue extracts were analyzed for the expression and activity of MMP-2.


RESULTS
The data showed that blocking the activity of all MMPs with relatively high inhibitor concentrations completely prevented the conversion of pro-MMP-2 into its active form and that the level of protein was decreased. Selective inhibition of the activity of gelatinases (MMP-2 and MMP-9) by using low inhibitor concentrations, however, induced a higher level of active MMP-2 and increased its expression significantly.


CONCLUSIONS
The current observations indicate that selective inhibitors of MMPs affect the expression and activity of MMP-2, thus providing clues regarding the differing effects such inhibitors appear to have when applied in vivo.
Kerkvliet
Erika H M
EH
Department of Periodontology, Academic Center for Dentistry Amsterdam, University of Amsterdam, Amsterdam, The Netherlands.
Jansen
Ineke D C
ID
Schoenmaker
Ton A M
TA
Docherty
Andy J P
AJ
Beertsen
Wollter
W
Everts
Vincent
V
D000818:Animals; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D061965:Matrix Metalloproteinase Inhibitors; D008970:Molecular Weight; D010521:Periosteum / Q000166:cytology; D011817:Rabbits
D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D020778:Matrix Metalloproteinase 2