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Effects of TGF-β1 on the proliferation and differentiation of human periodontal ligament cells and a human periodontal ligament stem/progenitor cell line

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Abstract

Periodontal ligament (PDL) is a specialized connective tissue that influences the lifespan of the tooth. Transforming growth factor-β1 (TGF-β1) is a multifunctional cytokine, but little is known about the effects of TGF-β1 on PDL cells. Our aim has been to demonstrate the expression of TGF-β1 in rat PDL tissues and to evaluate its effects on the proliferation and gene expression in human PDL cells (HPLCs) and a human PDL stem/progenitor cell line, line 1-11, that we have recently developed. The expression of TGF-β1 in the entire PDL tissue was confirmed immunohistochemically, and both HPLCs and cell line 1-11 expressed mRNA from the TGF-β1, TGF-β type I receptor, and TGF-β type II receptor genes. Although exogenous TGF-β1 stimulated the proliferation of HPLCs, it did not upregulate the expression of alpha-smooth muscle actin (α-SMA), type I collagen (Col I), or fibrillin-1 (FBN1) mRNA or of α-SMA protein in HPLCs, whereas expression for these genes was attenuated by an anti-TGF-β1 neutralizing antibody. In contrast, exogenous TGF-β1 reduced the proliferation of cell line 1-11, although it upregulated the expression of α-SMA, Col I, and FBN1 mRNA and of α-SMA protein in this cell line. In addition, interleukin-1 beta stimulation significantly reduced the expression of TGF-β1 mRNA and protein in HPLCs. Thus, TGF-β1 seems to play an important role in inducing fibroblastic differentiation of PDL stem/progenitor cells and in maintaining the PDL apparatus under physiological conditions.

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References

  • Agarwal S, Chandra CS, Piesco NP, Langkamp HH, Bowen L, Baran C (1998) Regulation of periodontal ligament cell functions by interleukin-1beta. Infect Immun 66:932–937

    CAS  PubMed  Google Scholar 

  • Andriamanalijaona R, Felisaz N, Kim SJ, King-Jones K, Lehmann M, Pujol JP, Boumediene K (2003) Mediation of interleukin-1beta-induced transforming growth factor beta1 expression by activator protein 4 transcription factor in primary cultures of bovine articular chondrocytes: possible cooperation with activator protein 1. Arthritis Rheum 48:1569–1581

    Article  CAS  PubMed  Google Scholar 

  • Arora PD, McCulloch CA (1994) Dependence of collagen remodelling on alpha-smooth muscle actin expression by fibroblasts. J Cell Physiol 159:161–175

    Article  CAS  PubMed  Google Scholar 

  • Arora PD, Narani N, McCulloch CA (1999) The compliance of collagen gels regulates transforming growth factor-beta induction of alpha-smooth muscle actin in fibroblasts. Am J Pathol 154:871–882

    CAS  PubMed  Google Scholar 

  • Beertsen W, McCulloch CAG, Sodek J (1997) The periodontal ligament: a unique, multifunctional connective tissue. Periodontology 13:20–40

    Article  CAS  Google Scholar 

  • Birgel M, Gottschling-Zeller H, Rohrig K, Hauner H (2000) Role of cytokines in the regulation of plasminogen activator inhibitor-1 expression and secretion in newly differentiated subcutaneous human adipocytes. Arterioscler Thromb Vasc Biol 20:1682–1687

    CAS  PubMed  Google Scholar 

  • Brady TA, Piesco NP, Buckly MJ, Langkamp HH, Bowen LL, Agarwal S (1998) Autoregulation of periodontal ligament cell phenotype and functions by transforming growth factor-beta1. J Dent Res 77:1779–1790

    Article  CAS  PubMed  Google Scholar 

  • Chai Y, Jiang X, Ito Y, Bringas P Jr, Han J, Rowitch DH, Soriano P, Mcmahon AP, Sucov HM (2000) Fate of the mammalian cranial neural crest during tooth and mandibular morphogenesis. Development 127:1671–1679

    CAS  PubMed  Google Scholar 

  • Dallas SL, Miyazono K, Skerry TM, Mundy GR, Bonewald LF (1995) Dual role for the latent transforming growth factor-β binding protein in storage of latent TGF-β in the extracellular matrix and as a structural matrix protein. J Cell Biol 131:539–549

    Article  CAS  PubMed  Google Scholar 

  • Freeman E (1994) Oral histology: development, structure, and function. In: Ten Cate AR (ed) Periodontium. Mosby, St. Louis, pp 276–312

    Google Scholar 

  • Fujii S, Maeda H, Wada N, Kano Y, Akamine A (2006) Establishing and characterizing human periodontal ligament fibroblasts immortalized by SV40T-antigen and hTERT gene transfer. Cell Tissue Res 324:117–125

    Article  CAS  PubMed  Google Scholar 

  • Fujii S, Maeda H, Wada N, Tomokiyo A, Saito M, Akamine A (2008) Investigating a clonal human periodontal ligament progenitor/stem cell line in vitro and in vivo. J Cell Physiol 215:743–749

    Article  CAS  PubMed  Google Scholar 

  • Fujita T, Shiba H, Thomas EVD, Kurihara H (2004) Differential effects of growth factors and cytokines on the synthesis of SPARC, DNA, fibronectin and alkaline phosphatase activity in human periodontal ligament cells. Cell Biol Int 28:281–286

    Article  CAS  PubMed  Google Scholar 

  • Gemmell E, Marshall RI, Seymour GJ (1997) Cytokine and prostaglandins in immune homeostasis and tissue destruction in periodontal disease. Periodontol 2000 14:112–143

    Article  CAS  PubMed  Google Scholar 

  • Ghosh AK, Yuan W, Mori Y, Varga J (2000) Smad-dependent stimulation of type I collagen gene expression in human skin fibroblasts by TGF-beta involves functional cooperation with p300/CBP transcriptional coactivators. Oncogene 19:3546–3555

    Article  CAS  PubMed  Google Scholar 

  • Godin I, Wylie CC (1991) TGF beta 1 inhibits proliferation and has a chemotropic effect on mouse primordial germ cells in culture. Development 113:1451–1457

    CAS  PubMed  Google Scholar 

  • Heredia A, Villena J, Romaris M, Molist A, Bassols A (1996) The effect of TGF-beta 1 on cell proliferation and proteoglycan production in human melanoma cells depends on the degree of cell differentiation. Cancer Lett 109:39–47

    Article  CAS  PubMed  Google Scholar 

  • Hou Y, Mao Z, Wei X, Lin L, Chen L, Wang H, Fu X, Zhang J, Yu C (2009) Effects of transforming growth factor-β1 and vascular endothelial growth factor 165 gene transfer on Achilles tendon healing. Matrix Biol 28:324–335

    Article  CAS  PubMed  Google Scholar 

  • Isogai Z, Ono RN, Ushiro S, Keene DR, Chen Y, Mazzieri R, Charbonneau NL, Reinhardt DP, Rifkin DB, Sakai LY (2003) Latent transforming growth factor-β binding protein 1 interacts with fibrillin and is a microfibril-associated protein. J Biol Chem 278:2750–2757

    Article  CAS  PubMed  Google Scholar 

  • Katagiri T, Lee T, Takeshima H, Suda T, Tanaka H, Omura S (1990) Transforming growth factor-β modulates proliferation and differentiation of mouse clonal osteoblastic MC3T3-E1 cells depending on their maturation stages. Bone Miner 11:285–293

    Article  CAS  PubMed  Google Scholar 

  • Kenney MC, Zorapapel N, Atilano S, Chwa M, Ljubimov A, Brown D (2003) Insulin-like growth factor-I (IGF-I) and transforming growth factor-beta (TGF-beta) modulate tenascin-C and fibrillin-1 in bullous keratopathy stromal cells in vitro. Exp Eye Res 77:537–546

    Article  CAS  PubMed  Google Scholar 

  • Kingsley DM (1994) The TGF-beta superfamily: new members, new receptors and new genetic tests of function in different organisms. Genes Dev 8:133–146

    Article  CAS  PubMed  Google Scholar 

  • Kissin EY, Lemarie R, Korn JH, Lafyatis R (2002) Transforming growth factor beta induces fibroblast fibrillin-1 matrix formation. Arthritis Rheum 46:3000–3009

    Article  CAS  PubMed  Google Scholar 

  • Liu Y, Zheng Y, Ding G, Fang D, Zhang C, Bartold PM, Gronthos S, Shi S, Wang S (2008) Periodontal ligament stem cell-mediated treatment for periodontitis in miniature swine. Stem Cells 26:1065–1073

    Article  PubMed  Google Scholar 

  • Luo DD, Fielding C, Phillips A, Fraser D (2009) Interleukin-1 beta regulates proximal tubular cell transforming growth factor beta-1 signalling. Nephrol Dial Tranplant 24:2655–2665

    Article  CAS  Google Scholar 

  • Maeda H, Nakano T, Tomokiyo A, Fujii S, Wada N, Monnouchi S, Hori K, Akamine A (2010) Mineral trioxide aggregate induces bone morphogenetic protein-2 expression and calcification in human periodontal ligament cells. J Endod 36:743–749

    Article  Google Scholar 

  • Masada MP, Persson JS, Kenney R, Page C, Allison AC (1990) Measurement of interleukin-1 alpha and -1 beta in gingival crevicular fluid: implications for periodontal disease. J Periodontal Res 25:156–163

    Article  CAS  PubMed  Google Scholar 

  • Matthew B, Naveen Y, Hung P, Michael T, Chang J (2002) Flexor tendon healing in vitro: effects of TGF-β on tendon cell collagen production. J Hand Surg 27:615–620

    Article  Google Scholar 

  • Nagatomo K, Komaki M, Sekiya I, Sakaguchi Y, Noguchi K, Oda S, Murata T, Ishikawa I (2006) Stem cell properties of human periodontal ligament cells. J Periodontal Res 41:303–310

    Article  CAS  PubMed  Google Scholar 

  • Narayanan AS, Page RC (1983) Connective tissues of the periodontium: a summary of current work. Coll Relat Res 3:33–64

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Okubo K, Kobayashi M, Takiguchi T, Takada T, Ohazama A, Okamatsu Y, Hasegawa K (2003) Participation of endogenous IGF-I and TGF-β1 with enamel matrix derivative-stimulated cell growth in human periodontal ligament cells. J Periodont Res 38:1–9

    Article  CAS  PubMed  Google Scholar 

  • Ono Y, Sensui H, Okutsu S, Nagatomi R (2007) Notch2 negatively regulates myofibroblastic differentiation of myoblasts. J Cell Physiol 210:358–369

    Article  CAS  PubMed  Google Scholar 

  • Seo BM, Miuram GS, Bartold PM, Batouli S, Brahim J, Young M, Robey PG, Wang CY, Shi S (2004) Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet 364:149–155

    Article  CAS  PubMed  Google Scholar 

  • Shi Y, Massague J (2003) Mechanisms of TGF-β signaling from cell membrane to the nucleus. Cell 113:685–700

    Article  CAS  PubMed  Google Scholar 

  • Sonoyama W, Liu Y, Fang D, Yamaza T, Seo M, Zhang C, Liu H, Gronthos S, Wang CY, Shi S, Wang S (2006) Mesenchymal stem cell-mediated functional tooth regeneration in swine. PLoS ONE 1:1–8

    Article  Google Scholar 

  • Tomokiyo A, Maeda H, Fujii S, Wada N, Shima K, Akamine A (2008) Development of a multipotent clonal human periodontal ligament cell line. Differentiation 76:337–347

    Article  CAS  PubMed  Google Scholar 

  • Worapamorn W, Haase HR, Li H, Bartold PM (2001) Growth factors and cytokines modulate gene expression of cell-surface proteoglycans in human periodontal ligament cells. J Cell Physiol 186:448–456

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Endodontology and Operative Dentistry, Division of Oral Rehabilitation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Shinsuke Fujii, Hidefumi Maeda, Atsushi Tomokiyo, Satoshi Monnouchi, Kiyomi Hori, Naohisa Wada & Akifumi Akamine

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  1. Shinsuke Fujii
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  2. Hidefumi Maeda
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  3. Atsushi Tomokiyo
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  4. Satoshi Monnouchi
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  5. Kiyomi Hori
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  6. Naohisa Wada
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  7. Akifumi Akamine
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Correspondence to Hidefumi Maeda.

Additional information

This work was supported by grants-in-aid (projects 21390510, 21791942, 22390359, and 22592123) for scientific research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan.

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Fujii, S., Maeda, H., Tomokiyo, A. et al. Effects of TGF-β1 on the proliferation and differentiation of human periodontal ligament cells and a human periodontal ligament stem/progenitor cell line. Cell Tissue Res 342, 233–242 (2010). https://doi.org/10.1007/s00441-010-1037-x

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  • DOI: https://doi.org/10.1007/s00441-010-1037-x

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