title: BMP-2 regulates the formation of oral sulcus in mouse tongue by altering the balance between TIMP-1 and MMP-13.
abstract: The aim of this study is to investigate whether BMP-2 regulates the oral sulcus formation of mouse embryonic tongue by modifying the expression of TIMP and MMP. The BMP-2 siRNA induced a 180% increase in the depth of oral sulcus cavity (P < 0.01) by stimulating the invagination of oral sulcus into the mesenchymal tissues consisting of tongue floor, whereas the recombinant BMP-2 suppressed the process in the organ culture system of mouse embryonic tongue. The BMP-2 siRNA induced a 60% decrease in the expression of TIMP-1 mRNA (P < 0.05) and a drastic decline in TIMP-1 protein was observed around the oral sulcus in the BMP-2 siRNA treated mandibles. The recombinant BMP-2 induced a 220% increases in the expression of TIMP-1 mRNA and the area of the immunostaining for TIMP-1 around the oral sulcus was larger in the mandibles treated with the recombinant BMP-2 than the vehicle. The BMP-2 siRNA induced a 60% increase in the expression of MMP-13 protein and a marked increase in the staining intensity for MMP-13 was observed in the epithelial region of the BMP-2 siRNA treated mandibles. The recombinant BMP-2 induced a 70% decrease in the expression of MMP-13 mRNA and the decrease was mainly observed in the tissues around oral sulcus. The expressions of BMP-2, TIMP-1, and MMP-13 were verified in the tissues around in vivo developing oral sulcus at E11, 12, and 13 by immunohistochemistry. These results suggest that BMP-2 regulates the formation of oral sulcus by altering the balance between TIMP-1 and MMP-13.
authors.affiliation: Department of Orthodontics, Tsurumi University School of Dental Medicine, Tsurumi-ku, Yokohama, Japan.
authors.forename: Tadayoshi
authors.initials: T
authors.lastname: Fukui
authors.forename: Takeo
authors.initials: T
authors.lastname: Suga
authors.forename: Ryo-Hei
authors.initials: RH
authors.lastname: Iida
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Morito
authors.forename: Xianghong
authors.initials: X
authors.lastname: Luan
authors.forename: Thomas G H
authors.initials: TG
authors.lastname: Diekwisch
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Akira
authors.initials: A
authors.lastname: Yamane
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism* / Q000494:pharmacology; D007150:Immunohistochemistry; D008334:Mandible / Q000196:embryology / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D009024:Morphogenesis; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D019714:Tissue Inhibitor of Metalloproteinases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D014059:Tongue / Q000196:embryology* / Q000378:metabolism
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1; D019714:Tissue Inhibitor of Metalloproteinases; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse