Transforming Growth Factor-ß1 (TGF-ß1) immunoreactivity in heterotopic grafts of adult dental apical papilla.

Telmo José Mezadri, David Rivero Tames, Xana Raquel Ortolan, José Angel Armengol


Objective: To analyze the expression of transforming growth factor-ß1 in heterotopic grafts of adult dental apical papillae. Methodology: Adult apical papillae of Wistar rats were grafted in the ear of the same donor rats. 1, 3, 7 and 14 days after grafting, rats were perfused and the tissue containing the graft was processed for histological conventional technique and for immunohistochemical detection of transforming growth factor-ß1. Results: Heterotopically grafted apical papilla developed osteoid dentine. In an early post-grafting stage, odontoblast-like cells organized themselves in palisade and synthesized dentine. However, newly formed dentine possessed the structural appearance of reactive osteoid dentine, which was systematically destroyed by the activity of osteoclaste-like cells. Transforming Growth Factor-ß1 was observed in mesenchymal cells, extracellular matrix of the graft and surrounding host tissue, while odontoblast-like cells were systematically devoid of immunoreactivity. Conclusion: The different expression of transforming growth factor-ß1 between normal tissue and grafted tissue development suggests that in heterotopic graft conditions the inflammatory mediation of the transforming growth factor-ß1 prevails against its morphogenetic role.


odontoblast, apical papilla,TGF-ß1, graft.


Gronthos S, Mankani M, Brahim J, Gehron Robey P, Shi S. Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci USA 2000; 97(25):13625–13630.

Komada Y, Yamane T, Kadota D, Isono K, Takakura N, Hayashi SI, Yamazaki H. Origins and properties of dental, thymic, and bone marrow mesenchymal cells and their stem cells. PLoS One 2012; 7(11): e46436.

Masthan KMK, Sankari SL, Babu NA, Gopalakrishnan T. Mistery inside the tooth: the dental pulp stem cells. J Clin Diag Res 2013; 7(5): 945-947.

Rai S, Kaur M, Kaur S. Applications of stem cells in interdisciplinary dentistry and beyond: an overview. Ann Med Health Sci Res 2013; 3(2): 245–254.

Kim RH, Mehrazarin S, Kang MK. Therapeutic Potential of Mesenchymal Stem Cells for Oral and Systemic Diseases. Dent Clin North Am 2012; 56(3):651–675.

Ibarretxe G, Crende O, Aurrekoetxea M, García-Murga V, Etxaniz J, Unda F. Neural Crest Stem Cells from Dental Tissues: A New Hope for Dental and Neural Regeneration. Stem Cells Int 2012:103503.

Nagano T, Oida S, Suzuki S, Iwata T. Yamakoshi Y, Ogata Y, Gomi K, Arai T, Fukae M. Porcine enamel protein fractions contain transforming growth factor-beta 1. J Periodontol 2006; 77(10):1688-1694.

Gao Y, Li D, Han T, Sun Y, Zhang J. TGF-beta1 and TGFBR1 are expressed in ameloblast and promote MMP20 expression. Anat Rec 2009; 292(6):885-890.

Ripamonti U, Petit J-C, Teare J. Cementogenesis and the induction of periodontal tissue regeneration by osteogenic proteins of transforming growth factor-ß superfamily. J Period Res 2009; 44(2):141-152.

Lee DS, Yoon WJ, Cho ES, Kim HJ, Gronostajski RM, Cho M, Park. JC. Crosstalk between Nuclear Factor I-C and Transforming Growth Factor-b1 Signaling Regulates Odontoblast Differentiation and Homeostasis. PLoS One 2011; 6(12):e29160.

Oka S, Oka K, Xu X, Sasaki T, Bringas P Jr, Chai Y. Cell autonomous requirement for TGF-b signaling during odontoblast differentiation and dentin matrix formation. Mech Dev. 2007; 124(6):409–415.

Li J, Huang X, Xu X, Mayo J, Bringas P Jr, Jiang R, Wang S, Chai Y. SMAD4-mediated WNT signaling controls the fate of cranial neural crest cells during tooth morphogenesis. Development 2011; 138(10):1977–1989.

Wang XP, Suomalainen M, Felszeghy S, Zelarayan LC, Alonso MT, Plikus MV, Maas RL, Chuong CM, Schimmang T, Thesleff I. An integrated gene regulatory network controls stem cell proliferation in teeth. PLoS Biol 2007; 5(6):1324-1333.

Zhao H, Li S, Han D, Kaartinen V, Chai Y. Alk5 Mediated Transforming Growth Factor β Signaling Acts Upstream of Fibroblast Growth Factor 10 To Regulate the Proliferation and Maintenance of Dental Epithelial Stem Cells. Mol Cell Biol 2011; 31(10):2079-2089.

Huang GTJ. Dental Pulp and Dentin Tissue Engineering and Regeneration – Advancement and Challenge. Front Biosci (Elite Ed) 2011; 1(3):788–800.

Mezadri TJ, Tames DR, Boabaid F, Armengol JA. Development of tooth germ heterotopically grafted within the ear skin. An histological study in the rat. Med Oral 2004; 9(3):243-252.

Waskievicz P, Medeiros TCC, Mezadri TJ, Brandalise VA, Tames DR. Transplante autólogo da papila dental vestibular e lingual de incisivo de rato adulto no pavilhão auditivo. Braz Oral Res 2011; 1:151-172.

Holtgrave EA, Donath K. Response of odontoblast-like cells to hydroxyapatite ceramic granules. Biomaterials 1995; 16(2):155-9.

Moehl T, Ripamonti U. Primate dentine extracellular matrix induces bone differentiation in heteropic sites of Baboom (Papio ursinus). J Periodontal Res 1992; 27(2):92-96.

Ishizeki K, Nawa T, Sugawara M. Calcification capacity of dental papilla mesenchymal cells transplanted in the isogenic mouse spleen. Anat Rec 1990; 226(3): 279-287.

Higashi T, Okamoto H. Characteristics and effects of calcified degenerative zones on the formation of hard tissue barriers in amputed canine dental pulp. J Endod 1996; 22(4):168-172.

Shimono M. Influences of 4-meta/MMA-TBB adhesive resin on osteodentinognesis of transplanted rabbit dental pulp in vivo: immunohistochemical and electron microscopic studies. Bull Tokyo Dent Coll 1999; 40:129-138.

Kulkarni AB, Huh Ch-G, Becker D, Geisert A, Lyght M, Flanderst KC, Roberts AB, Sporn MB, Ward JM, Karlsson S. Transforming growth factor 181 null mutation in mice causes excessive inflammatory response and early death. Proc Natl Acad Sci USA 1993; 90(2):770-774.

Leask A, Parapuram SK, Shi-wen X, Abraham DJ. Connective tissue growth factor (CTGF, CCN2) gene regulation: a potent clinical bio-marker of fibroproliferative disease? J Cell Commun Signal 2009; 3(2):89–94.

Nakashima M, Nagasawa H, Yamada Y, Reddi AH. Regulatory role of transforming growth factor-beta, bone morphogenetic protein-2 and protein-4 on gene expression of extracellular matrix proteins and differentiation of dental pulp cells. Dev Biol 1994;162(1):18-28.

Klopcic B, Maass T, Meyer E, Lehr HA, Metzger D, Chambon P, Mann A, Blessing M. TGF-beta superfamily signaling is essential for tooth and hair morphogenesis and differentiation. Eur J Cell Biol 2007; 86 (11-12): 781–799.

Shiba H, Fujita T, Doi N, Nakamura S, Nakanishi K, Takemoto T, Hino T, Noshiro M, Kawamoto T, Kurihara H, Kato Y. Differential effects of various growth factors and cytokines on the syntheses of DNA, type I collagen, laminin, fibronectin, osteonectin/secreted protein, acidic and rich in cysteine (SPARC), and alkaline phosphatase by human pulp cells in culture. J Cell Physiol 1998; 174(2): 194–205.

Tsuchiya T, Sharma R, Tye CE, Sugiyama T, Barlett JD. Transforming growth factor-ß1 expression is up regulated in maturation-stage enamel organ and may induce ameloblast apoptosis. Eur J Oral Sci 2009; 117(2):105-112.

Haruyama N, Thyagarajan T, Skobe Z, Wright JT, Septier D, Sreenath TL, Goldberg M, Kulkarni AB. Overexpression of transforming growth factor-beta1 in teeth results in detachment of ameloblasts and enamel defects. Eur J Oral Sci 2006; 114 (1): 30–34.

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