Growth and differentiation factors (GDF) 5, 6, and 7 are known to play roles in tendon and ligament formation, and are therefore probably involved in the formation of periodontal ligament. In this study, we sought to determine temporal and spatial expression of GDF-5, -6, and -7 mRNA in developing periodontal tissue of rat molars using in situ hybridization. GDF gene expression in the periodontal ligament was first detected in cells associated with the initial process of periodontal ligament fiber bundle formation. Gene signals were also detected in cells located along the alveolar bone and cementum surfaces, the insertion sites of periodontal ligaments, during the course of root formation. GDF expression in these cells were down-regulated after completion of root formation. Our results appeared to suggest the involvement of GDF-5, -6, and -7 in the formation of the dental attachment apparatus.
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References
1.
Åberg T, Wozney J, Thesleff I -1997-. Expression patterns of bone morphogenetic proteins -Bmps- in the developing mouse tooth suggest roles in morphogenesis and cell differentiation. Dev Dyn210:383–396.
2.
Ahrens M, Ankenbauer T, Schroder D, Hollnagel A, Mayer H, Gross G -1993-. Expression of human bone morphogenetic proteins-2 or -4 in murine mesenchymal progenitor C3H10T1/2 cells induces differentiation into distinct mesenchymal cell lineages. DNA Cell Biol12:871–880.
3.
Aspenberg P, Forslund C -1999-. Enhanced tendon healing with GDF5 and 6. Acta Orthop Scand70:51–54.
4.
Bègue-Kirn C, Smith AJ, Loriot M, Kupferle C, Ruch JV, Lesot H -1994-. Comparative analysis of TGFbetas, BMPs, IGF1, msxs, fibronectin, osteonectin and bone sialoprotein gene expression during normal and in vitro-induced odontoblast differentiation. Int J Dev Biol38:405–420.
5.
Celeste AJ, Iannazzi JA, Taylor RC, Hewick RM, Rosen V, Wang EA, et al. -1990-. Identification of transforming growth factor beta family members present in bone-inductive protein purified from bovine bone. Proc Natl Acad Sci USA87:9843–9847.
6.
Cox K, Rosen V -1996-. Ultrastructural analysis of cells and extracellular matrix at the site of recombinant human BMP-12 induced tendon/ligament-like tissue in the rat quadriceps muscle -abstract-. J Bone Miner Res11:S401.
7.
Furuya K, Nifuji A, Rosen V, Noda M -1999-. Effects of GDF7/BMP12 on proliferation and alkaline phosphatase expression in rat osteoblastic osteosarcoma ROS 17/2.8 cells. J Cell Biochem72:177–180.
8.
Gruber R, Mayer C, Schulz W, Graninger W, Peterlik M, Watzek G, et al. -2000-. Stimulatory effects of cartilage-derived morphogenetic proteins 1 and 2 on osteogenic differentiation of bone marrow stromal cells. Cytokine12:1630–1638.
9.
Heikinheimo K -1994-. Stage-specific expression of decapentaplegic-Vg-related genes 2, 4, and 6 -bone morphogenetic proteins 2, 4, and 6- during human tooth morphogenesis. J Dent Res73:590–597.
10.
Helder MN, Karg H, Bervoets TJ, Vukicevic S, Burger EH, D’Souza RN, et al. -1998-. Bone morphogenetic protein-7 -osteogenic protein-1, OP-1- and tooth development. J Dent Res77:545–554.
11.
Hogan BL -1996-. Bone morphogenetic proteins: multifunctional regulators of vertebrate development. Genes Dev10:1580–1594.
12.
Inada M, Katagiri T, Akiyama S, Namiki M, Komaki M, Yamaguchi A, et al. -1996-. Bone morphogenetic protein-12 and -13 inhibit terminal differentiation of myoblasts, but do not induce their differentiation into osteoblasts. Biochem Biophys Res Commun222:317–322.
13.
Katagiri T, Yamaguchi A, Komaki M, Abe E, Takahashi N, Ikeda T, et al. -1994-. Bone morphogenetic protein-2 converts the differentiation pathway of C2C12 myoblasts into the osteoblast lineage -published erratum in J Cell Biol 128:713, 1995-. J Cell Biol127:1755–1766.
14.
Lou J, Tu Y, Ludwig JF, Zhang J, Manske PR -1999-. Effect of bone morphogenetic protein-12 gene transfer on mesenchymal progenitor cells. Clin Orthop369:333–339.
15.
Lou J, Tu Y, Burns M, Silva MJ, Manske P -2001-. BMP-12 gene transfer augmentation of lacerated tendon repair. J Orthop Res19:1199–1202.
16.
Lyons KM, Pelton RW, Hogan BL -1990-. Organogenesis and pattern formation in the mouse: RNA distribution patterns suggest a role for bone morphogenetic protein-2A -BMP-2A-. Development109:833–844.
17.
Morotome Y, Goseki-Sone M, Ishikawa I, Oida S -1998-. Gene expression of growth and differentiation factors-5, -6, and -7 in developing bovine tooth at the root forming stage -published erratum appears in Biochem Biophys Res Commun 246:925, 1998-. Biochem Biophys Res Commun244:85–90.
18.
Oida S, Morotome Y, Nakamura T, Terashima T -1997-. Molecular cloning of PCR amplified BMP-related genes -GDF-5, 6 and 7- from rat tooth cells using modified pBluescript SK+ vector. J Hard Tissue Biol6:16–20.
19.
Ripamonti U, Heliotis M, Rueger DC, Sampath TK -1996-. Induction of cementogenesis by recombinant human osteogenic protein-1 -hOP-1/BMP-7- in the baboon -Papio ursinus-. Arch Oral Biol41:121–126.
20.
Rosen V, Nove J, Song JJ, Thies RS, Cox K, Wozney JM -1994-. Responsiveness of clonal limb bud cell lines to bone morphogenetic protein 2 reveals a sequential relationship between cartilage and bone cell phenotypes. J Bone Miner Res9:1759–1768.
21.
Rutherford RB, Wahle J, Tucker M, Rueger D, Charette M -1993-. Induction of reparative dentine formation in monkeys by recombinant human osteogenic protein-1. Arch Oral Biol38:571–576.
22.
Schroeder HE -1986-. The periodontium. Handbook of microscopic anatomy. Vol. 5. Berlin: Springer-Verlag.
23.
Storm EE, Huynh TV, Copeland NG, Jenkins NA, Kingsley DM, Lee SJ -1994-. Limb alterations in brachypodism mice due to mutations in a new member of the TGFbeta-superfamily. Nature368:639643. Comment on: Nature 368:587–588.
24.
Takahashi H, Ikeda T -1996-. Transcripts for two members of the transforming growth factor-beta superfamily BMP-3 and BMP-7 are expressed in developing rat embryos. Dev Dyn207:439–449.
25.
Thesleff I -1995-. Homeobox genes and growth factors in regulation of craniofacial and tooth morphogenesis. Acta Odontol Scand53:129–134.
26.
Urist MR -1965-. Bone: formation by autoinduction. Science150:893–899.
27.
Vainio S, Karavanova I, Jowett A, Thesleff I -1993-. Identification of BMP-4 as a signal mediating secondary induction between epithelial and mesenchymal tissues during early tooth development. Cell75:45–58.
28.
Valcourt U, Ronziere MC, Winkler P, Rosen V, Herbage D, Mallein-Gerin F -1999-. Different effects of bone morphogenetic proteins 2, 4, 12, and 13 on the expression of cartilage and bone markers in the MC615 chondrocyte cell line. Exp Cell Res251:264–274.
29.
Wolfman NM, Hattersley G, Cox K, Celeste AJ, Nelson R, Yamaji N, et al. -1997-. Ectopic induction of tendon and ligament in rats by growth and differentiation factors 5, 6, and 7, members of the TGF-beta gene family. J Clin Invest100:321–330.
30.
Wozney JM, Rosen V, Celeste AJ, Mitsock LM, Whitters MJ, Kriz RW, et al. -1988-. Novel regulators of bone formation: molecular clones and activities. Science242:1528–1534.
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