Identification of endoglin-dependent BMP-2-induced genes in the murine periodontal ligament cell line PDL-L2

Journal of Molecular Signaling

Takashi Inui¹  Osamu Ishibashi¹ 

[1] Laboratory of Biological Macromolecules, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai 599-8531, Japan

关键词: Endoglin;    Bone morphogenetic protein;    Periodontal ligament;   

Others  :  802214
DOI  :  10.1186/1750-2187-9-5

 received in 2014-01-29, accepted in 2014-06-10,  发布年份 2014

【 摘 要 】

Background

The periodontal ligament (PDL), connective tissue located between the cementum of teeth and alveolar bone of the mandibula, plays an important role in the maintenance and regeneration of periodontal tissues. We reported previously that endoglin was involved in the BMP-2-induced osteogenic differentiation of mouse PDL cells, which is associated with Smad-2 phosphorylation but not Smad-1/5/8 phosphorylation. In this study, to elucidate the detailed mechanism underlying the BMP-2 signalling pathway unique to PDL cells, we performed a microarray analysis to identify BMP-2-inducible genes in PDL-L2 cells, a mouse PDL-derived cell line, with or without endoglin knockdown.

Findings

Sixty-four genes were upregulated more than twofold by BMP-2 in PDL-L2 cells. Of these genes, 11 were endoglin-dependent, including Id4, which encodes ID4, a helix-loop-helix transcription factor closely associated with TGF-β signaling and osteoblast differentiation. The endoglin-dependent induction of ID4 by BMP-2 was also verified at a protein level.

Conclusion

Our findings indicate that ID4 could be a signal mediator involved in the BMP-2-induced endoglin-dependent osteogenic differentiation of PDL cells.

【 授权许可】

   
2014 Ishibashi and Inui; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Berkovitz BKB, Shore RC: Cells of the periodontal ligament. In The periodontal ligament in health and disease. 2nd edition. Edited by Berkovitz BKB, Moxham BJ, Newman HJ. London: Mosby-Wolfe; 1995:9-33.
• [2]Beertsen W, McCulloch CA, Sodek J: The periodontal ligament: a unique, multifunctional connective tissue. Periodontol 2000 1997, 13:20-40.
• [3]Saito Y, Yoshizawa T, Takizawa F, Ikegame M, Ishibashi O, Okuda K, Hara K, Ishibashi K, Obinata M, Kawashima H: A cell line with characteristics of the periodontal ligament fibroblasts is negatively regulated for mineralization and Runx2/Cbfa1/Osf2 activity, part of which can be overcome by bone morphogenetic protein-2. J Cell Sci 2002, 115:4191-4200.
• [4]Yoshizawa T, Takizawa F, Iizawa F, Ishibashi O, Kawashima H, Matsuda A, Endoh N, Kawashima H: Homeobox protein MSX2 acts as a molecular defense mechanism for preventing ossification in ligament fibroblasts. Mol Cell Biol 2004, 24:3460-3472.
• [5]Ishibashi O, Ikegame M, Takizawa F, Yoshizawa T, Matsuda A, Ali MM, Iizawa F, Mera H, Kawashima H: Endoglin is involved in BMP-2-induced osteogenic differentiation of periodontal ligament cells through a pathway independent of Smad-1/5/8 phosphorylation. J Cell Physiol 2010, 222:465-473.
• [6]Quackenbush EJ, Letarte M: Identification of several cell surface proteins of non-T, non-B acute lymphoblastic leukemia by using monoclonal antibodies. J Immunol 1985, 134:1276-1285.
• [7]Fonsatti E, Del Vecchio L, Altomonte M, Sigalotti L, Nicotra MR, Coral S, Natali PG, Maio M: Endoglin: An accessory component of the TGF-beta-binding receptor-complex with diagnostic, prognostic, and bioimmunotherapeutic potential in human malignancies. J Cell Physiol 2001, 188:1-7.
• [8]Pérez-Gómez E, Del Castillo G, Juan Francisco S, López-Novoa JM, Bernabéu C, Quintanilla M: The role of the TGF-β coreceptor endoglin in cancer. Scientific World J 2010, 10:2367-2384.
• [9]Bourdeau A, Dumont DJ, Letarte M: A murine model of hereditary hemorrhagic telangiectasia. J Clin Invest 1999, 104:1343-1351.
• [10]McAllister KA, Grogg KM, Johnson DW, Gallione CJ, Baldwin MA, Jackson CE, Helmbold EA, Markel DS, McKinnon WC, Murrell J, McCormick MK, Pericak-Vance MA, Heutink P, Oostra BA, Haitjema T, Westerman CJJ, Porteous ME, Guttmacher AE, Letarte M, Marchuk DA: Endoglin, a TGF-beta binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1. Nat Genet 1994, 8:345-351.
• [11]Li DY, Sorensen LK, Brooke BS, Urness LD, Davis EC, Taylor DG, Boak BB, Wendel DP: Defective angiogenesis in mice lacking endoglin. Science 1999, 284:1534-1537.
• [12]Arthur HM, Ure J, Smith AJ, Renforth G, Wilson DI, Torsney E, Charlton R, Parums DV, Jowett T, Marchuk DA, Burn J, Diamond AG: Endoglin, an ancillary TGF-b receptor, is required for extraembryonic angiogenesis and plays a key role in heart development. Dev Biol 2000, 217:42-53.
• [13]Ishibashi O, Inui T: Dataset of microarray analysis to identify endoglin-dependent bone morphogenetic protein-2-responsive genes in the murine periodontal ligament cell line PDL-L2. Genomics Data 2014, 2:24-26.
• [14]Kondo M, Cubillo E, Tobiume K, Shirakihara T, Fukuda N, Suzuki H, Shimizu K, Takehara K, Cano A, Saitoh M, Miyazono K: A role for Id in the regulation of TGF-beta-induced epithelial-mesenchymal transdifferentiation. Cell Death Differ 2004, 11:1092-1101.
• [15]Kulterer B, Friedl G, Jandrositz A, Sanchez-Cabo F, Prokesch A, Paar C, Scheideler M, Windhager R, Preisegger KH, Trajanoski Z: Gene expression profiling of human mesenchymal stem cells derived from bone marrow during expansion and osteoblast differentiation. BMC Genomics 2007, 8:70. BioMed Central Full Text
• [16]Tokuzawa Y, Yagi K, Yamashita Y, Nakachi Y, Nikaido I, Bono H, Ninomiya Y, Kanesaki-Yatsuka Y, Akita M, Motegi H, Wakana S, Noda T, Sablitzky F, Arai S, Kurokawa R, Fukuda T, Katagiri T, Schönbach C, Suda T, Mizuno Y, Okazaki Y: Id4, a new candidate gene for senile osteoporosis, acts as a molecular switch promoting osteoblast differentiation. PLoS Genet 2010, 6:e1001019.
• [17]Benezra R, Rafii S, Lyden D: The Id proteins and angiogenesis. Oncogene 2001, 20:8334-8341.
• [18]Bedford L, Walker R, Kondo T, van Crüchten I, King ER, Sablitzky F: Id4 is required for the correct timing of neural differentiation. Dev Biol 2005, 280:386-395.
• [19]Riechmann V, van Crüchten I, Sablitzky F: The expression pattern of Id4, a novel dominant negative helix-loop-helix protein, is distinct from Id1, Id2 and Id3. Nucleic Acids Res 1994, 22:749-755.
• [20]Pagliuca A, Bartoli PC, Saccone S, Della Valle G, Lania L: Molecular cloning of ID4, a novel dominant negative helix-loop-helix human gene on chromosome 6p21.3-p22. Genomics 1995, 27:200-203.
• [21]Rigolet M, Rich T, Gross-Morand MS, Molina-Gomes D, Viegas-Pequignot E, Junien C: cDNA cloning, tissue distribution and chromosomal localization of the human ID4 gene. DNA Res 1998, 5:309-313.
• [22]Liu KJ, Harland RM: Cloning and characterization of Xenopus Id4 reveals differing roles for Id genes. Dev Biol 2003, 264:339-351.
• [23]Kreider BL, Benezra R, Rovera G, Kadesch T: Inhibition of myeloid differentiation by the helix-loop-helix protein Id. Science 1992, 255:1700-1702.