title: Mineral trioxide aggregate inhibits osteoclastic bone resorption.
abstract: Mineral trioxide aggregate (MTA), a commonly used endodontic repair material, is useful for both basic and clinical research, and the effect of MTA on osteoblast differentiation has been well-defined. However, the effects of MTA on osteoclastic bone resorption are not fully understood. Hence, the aim of this study is to examine the effect of MTA solution in the regulation of osteoclast bone-resorbing activity using osteoclasts formed in co-cultures of primary osteoblasts and bone marrow cells. MTA solution dose-dependently reduced the total area of pits formed by osteoclasts. The reduction of resorption induced by 20% MTA treatment was due to inhibition of osteoclastic bone-resorbing activity and had no effect on osteoclast number. A 20% MTA solution disrupted actin ring formation, a marker of osteoclastic bone resorption, by reducing phosphorylation and kinase activity of c-Src, and mRNA expressions of cathepsin K and mmp-9. A high concentration of MTA solution (50%) induced apoptosis of osteoclasts by increasing the expression of Bim, a member of the BH3-only (Bcl-2 homology) family of pro-apoptotic proteins. Taken together, our results suggest that MTA is a useful retrofilling material for several clinical situations because it both stimulates osteoblast differentiation and inhibits bone resorption.
authors.affiliation: Division of Molecular Signaling and Biochemistry, Department of Biosciences, Center for Oral Biological Research, Kyushu Dental College, Fukuoka, Japan.
authors.forename: D
authors.initials: D
authors.lastname: Hashiguchi
authors.forename: H
authors.initials: H
authors.lastname: Fukushima
authors.forename: H
authors.initials: H
authors.lastname: Yasuda
authors.forename: W
authors.initials: W
authors.lastname: Masuda
authors.forename: M
authors.initials: M
authors.lastname: Tomikawa
authors.forename: K
authors.initials: K
authors.lastname: Morikawa
authors.forename: K
authors.initials: K
authors.lastname: Maki
authors.forename: E
authors.initials: E
authors.lastname: Jimi
mesh_terms: D017607:Aluminum Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis; D000072224:Bcl-2-Like Protein 11; D001854:Bone Marrow Cells / Q000187:drug effects; D001862:Bone Resorption / Q000517:prevention & control*; D000081247:CSK Tyrosine-Protein Kinase; D017610:Calcium Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D056657:Cathepsin K / Q000037:antagonists & inhibitors; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D004338:Drug Combinations; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D008815:Mice, Inbred Strains; D010006:Osteoblasts / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects*; D010087:Oxides / Q000494:pharmacology / Q000627:therapeutic use*; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D012387:Root Canal Filling Materials / Q000494:pharmacology / Q000627:therapeutic use*; D017640:Silicates / Q000494:pharmacology / Q000627:therapeutic use*; D019061:src-Family Kinases
chemical_list: D017607:Aluminum Compounds; D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D017610:Calcium Compounds; D004338:Drug Combinations; D061965:Matrix Metalloproteinase Inhibitors; D008565:Membrane Proteins; D010087:Oxides; D011518:Proto-Oncogene Proteins; D012387:Root Canal Filling Materials; D017640:Silicates; C086631:mineral trioxide aggregate; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; D056657:Cathepsin K