MMP-9 antisense oligodeoxynucleotide exerts an inhibitory effect on osteoclastic bone resorption by suppressing cell migration.
We have previously shown that matrix metalloproteinases (MMPs) play a role in osteoclastic bone resorption by facilitating migration of osteoclastic cells toward bone surface through matrices. Of MMPs identified so far, MMP-9 is likely the most important proteinase for the action, since osteoclasts express this enzyme at a tremendously high level. However, no direct evidence has been provided to demonstrate its contribution to bone resorption. In this study, to address this point, we used an MMP-9 antisense phosphothiorate oligodeoxynucleotide (S-ODN), which was shown to inhibit the protein synthesis of MMP-9 efficiently. We demonstrated that the antisense S-ODN inhibited osteoclastic pit formation on matrigel-coated dentine slices in a concentration-dependent manner with a maximum reduction of total pit volume by 53% at 10 microM. These results, taken together, suggest that MMP-9 is involved in osteoclastic bone resorption process possibly by facilitating migration of osteoclasts through proteoglican-rich matrices.
Ishibashi
Osamu
O
Division of Molecular and Cellular Pharmacology, Niigata University Graduate School of Dental and Medical Sciences, 2-5274 Gakkocho-dori, Niigata 951-8514, Japan.
Niwa
Satoru
S
Kadoyama
Keiichi
K
Inui
Takashi
T
D000818:Animals; D000831:Animals, Newborn; D001862:Bone Resorption / Q000201:enzymology* / Q000517:prevention & control; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics*; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology*; D010010:Osteoclasts / Q000187:drug effects*; D011817:Rabbits
D020319:Oligodeoxyribonucleotides, Antisense; D020780:Matrix Metalloproteinase 9