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Platelet-derived growth factor exerts disparate effects on odontoblast differentiation depending on the dimers in rat dental pulp cells

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Abstract

Platelet-derived growth factor (PDGF) has recently been demonstrated to control the expression of alkaline phosphatase and proteoglycan synthesis of odontoblastic cells in dental pulp tissues. Although PDGF appears to be closely related to dentinogenesis, much about the mode of action of PDGF on odontoblast differentiation remains unclear. In this study, we examined the effects of three PDGF dimers (PDGF AA, AB, and BB) on odontoblastic differentiation of dental pulp cells in long-term mineralized cultures. Dental pulp cells isolated from rat lower incisors were continuously treated with each of PDGF AA, AB, and BB in separate cultures for 20 days. The three PDGF dimers suppressed alkaline phosphatase activity, osteocalcin and calcium content, and the formation of dentin-like nodules. The expression of mRNA for dentin sialoprotein (DSP) in the cells was inhibited by PDGF AA treatment, whereas PDGF AB and BB treatment stimulated the expression of DSP, even though the dentin-like nodule formation was inhibited. Although the effects of PDGF on odontoblastic differentiation varied among the dimers, the cells expressed both PDGF α andβ receptors, whose quantities were similar. These results suggest that PDGF exerts diverse effects on odontoblastic differentiation depending on its dimeric form. These in vitro findings explain, at least in part, the in vivo action of PDGF in dentinogenesis during the repair process of damaged dental pulp.

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References

  • Andrew JG, Hoyland JA, Freemont AJ, Marsh DR (1995) Platelet-derived growth factor expression in normally healing human fractures. Bone 16:455–460

    CAS  PubMed  Google Scholar 

  • Aubin JE, Liu F, Malaval L, Gupta AK (1995) Osteoblast and chondroblast differentiation. Bone 17:77S–83S

    CAS  PubMed  Google Scholar 

  • Betsholtz C, Raines EW (1997) Platelet-derived growth factor: a key regulator of connective tissue cells in embryogenesis and pathogenesis. Kidney Int 51:1361–1369

    CAS  PubMed  Google Scholar 

  • Boskey A, Spevak L, Tan M, Doty SB, Butler WT (2000) Dentin sialoprotein (DSP) has limited effects on in vitro apatite formation and growth. Calcif Tissue Int 67:472–478

    Article  CAS  PubMed  Google Scholar 

  • Canalis E, Mccarthy TL, Centrella M (1989) Effects of platelet-derived growth factor on bone formation in vitro. J Cell Physiol 140:530–537

    CAS  PubMed  Google Scholar 

  • Centrella M, Mccarthy T, Kusmik WF, Canalis E (1991) Relative binding and biochemical effects of heterodimeric and homodimeric isoforms of platelet-derived growth factor in osteoblast-enriched cultures from fetal rat bone. J Cell Physiol 147:420–426

    CAS  PubMed  Google Scholar 

  • Centrella M, Mccarthy TL, Kusmik WF, Canalis E (1992) Isoform-specific regulation of platelet-derived growth factor activity and binding in osteoblast-enriched cultures from fetal rat bone. J Clin Invest 89:1076–1084

    CAS  PubMed  Google Scholar 

  • Chai Y, Bringas P Jr, Mogharei A, Shuler CF, Slavkin HC (1998) PDGF-A and PDGFR-α regulate tooth formation via autocrine mechanism during mandibular morphogenesis in vitro. Dev Dyn 213:500–511

    Article  CAS  PubMed  Google Scholar 

  • Chen P, Carrington JL, Paralkar VM, Pierce GF, Reddi AH (1992) Chick limb bud mesodermal cell chondrogenesis: inhibition by isoforms of platelet-derived growth factor and reversal by recombinant bone morphogenetic protein. Exp Cell Res 200:110–117

    CAS  PubMed  Google Scholar 

  • D’souza RN, Bronckers ALJJ, Happonen R-P, Doga DA, Farach-Carson MC, Butler WT (1992) Developmental expression of a 53 kDa dentin sialoprotein in rat tooth organs. J Histochem Cytochem 40:359–366

    Google Scholar 

  • D’souza RN, Cavender A, Sunavala G, Alvarez J, Ohshima T, Kulkarni AB, Macdougall M (1997) Gene expression patterns of murine dentin matrix protein 1 (Dmp 1) and dentin sialophosphoprotein (DSPP) suggest distinct developmental functions in vivo. J Bone Miner Res 12:2040–2049

    CAS  PubMed  Google Scholar 

  • Denholm IA, Moule AJ, Bartold PM (1998) The behaviour and proliferation of human dental pulp cell strains in vitro, and their response to the application of platelet-derived growth factorBB and insulin-like growth factor-1. Int Endodent J 31:251–258

    Article  CAS  Google Scholar 

  • George A, Srinivasan R, Thotakura SR, Liu K, Veis A (1999) Rat dentin matrix protein 3 is a compound protein of rat dentin sialoprotein and phosphophoryn. Connect Tissue Res 40:49–57

    CAS  PubMed  Google Scholar 

  • Gundberg CM, Hauschka PV, Lian JB, Gallop PM (1984) Osteocalcin: isolation, characterization and detection. Methods Enzymol 107:516–544

    CAS  PubMed  Google Scholar 

  • Hart CE, Forstrom JW, Kelly JD, Seifert RA, Smith RA, Ross R, Murray MJ, Bowen-Pope DF (1998) Two classes of PDGF receptor recognize different isoforms of PDGF. Science 240:1529–1531

    Google Scholar 

  • Heldin CH, Backstrom G, Ostman A, Hammacher A, Ronnstrand L, Rubin K, Nister M, Westermark B (1988) Binding of different dimeric forms of PDGF to human fibroblasts: evidence for two separate receptor types.EMBO J 7:1387–1393

    CAS  PubMed  Google Scholar 

  • Heldin CH, Ostman A, Westermark B (1993) Structure of platelet-derived growth factor: implications for functional properties. Growth Factors 8:245–252

    CAS  PubMed  Google Scholar 

  • Hock JM, Canalis E (1994) Platelet-derived growth factor enhances bone cell replication, but not differentiated function of osteoblasts. Endocrinology 134:1423–1428

    CAS  PubMed  Google Scholar 

  • Hsieh SC, Graves DT (1998) Pulse application of platelet-derived growth factor enhances formation of a mineralizing matrix while continuous application is inhibitory. J Cell Biochem 69:169–180

    Article  CAS  PubMed  Google Scholar 

  • Hu JC-C, Zhang C, Slavkin HC (1995) The role of platelet-derived growth factor in the development of mouse molars. Int J Dev Biol 39:939–945

    CAS  PubMed  Google Scholar 

  • Marden LJ, Fan RSP, Pierce GF, Reddi AH, Hollinger JO (1993) Platelet-derived growth factor inhibits bone regeneration induced by osteogenin, a bone morphogenetic protein, in rat craniotomy defects. J Clin Invest 92:2897–2905

    CAS  PubMed  Google Scholar 

  • Matsuoka J, Grotendorst GR (1989) Two peptides related to platelet-derived growth factor are present in human wound fluid. Proc Natl Acad Sci USA 86:4416–4420

    CAS  PubMed  Google Scholar 

  • Morrison-Graham K, Schatteman GC, Bork T, Bowen-Pope DF, Weston JA (1992) A PDGF receptor mutation in the mouse (Patch) perturbs the development of a non-neuronal subset of neural crest-derived cells. Development 115:133–142

    CAS  PubMed  Google Scholar 

  • Nakashima M (1992) The effects of growth factors on DNA synthesis, proteoglycan synthesis and alkaline phosphatase activity in bovine dental pulp cells. Archs Oral Biol 37:231–236

    CAS  Google Scholar 

  • Pierce GF, Mustoe TA, Senior RM, Reed J, Griffin GL, Thomason A, Deuel TF (1988) In vivo incisional wound healing augmented by platelet-derived growth factor and recombinant c-sis gene homodimeric proteins. J Exp Med 167:974–987

    CAS  PubMed  Google Scholar 

  • Raines EW, Ross R (1982) Platelet-derived growth factor. I. High yield purification and evidence for multiple forms. J Biol Chem 257:5154–5160

    CAS  PubMed  Google Scholar 

  • Rappolee DA, Brenner CA, Schultz R, Mark D, Werb Z (1988) Developmental expression of PDGF, TGF-α, and TGF-β genes in preimplantation mouse embryos. Science 241:1823–1825

    CAS  PubMed  Google Scholar 

  • Ross R, Raines EW, Bowen-Pope DF (1986) The biology of platelet-derived growth factor. Cell 46:155–169

    CAS  PubMed  Google Scholar 

  • Ross R, Bowen-Pope DF, Raines EW (1990) Platelet-derived growth factor and its role in health and disease. Philos Trans R Soc Lond Biol 12:155–169

    Google Scholar 

  • Russell WE, Wyk JJV, Pledger WJ (1984) Inhibition of the mitogenic effects of plasma by a monoclonal antibody to somatomedin C. Proc Natl Acad Sci USA 81:2389–2392

    CAS  PubMed  Google Scholar 

  • Rutherford RB, Trailsmith MD, Ryan ME, Charette MF (1992) Synergistic effects of dexamethasone on platelet-derived growth factor mitogenesis in vitro. Archs Oral Biol 37:139–145

    CAS  Google Scholar 

  • Stephenson DA, Mercola M, Anderson E, Wang C, Stiles CD, Bowen-Pope DF, Chapman VM (1991) Platelet-derived growth factor receptor α-subunit gene (Pdgfra) is deleted in the mouse patch (Ph) mutation. Proc Natl Acad Sci USA 88:6–10

    CAS  PubMed  Google Scholar 

  • Vogel A, Raines E, Kariya B, Rivest M-J, Ross R (1978) Coordinate control of 3T3 cell proliferation by platelet-derived growth factor and plasma components. Proc Natl Acad Sci USA 75:2810–2814

    CAS  PubMed  Google Scholar 

  • Yokose S, Kadokura H, Tajima Y, Fujieda K, Katayama I, Matsuoka T, Katayama T (2000) Establishment and characterization of a culture system for enzymatically released rat dental pulp cells. Calcif Tissue Int 66:139–144

    Article  CAS  PubMed  Google Scholar 

  • Yu X, Hsieh S-C, Bao W, Graves DT (1997) Temporal expression of PDGF receptors and PDGF regulatory effects on osteoblastic cells in mineralizing cultures. Am J Physiol 272:C1709–C1716

    CAS  PubMed  Google Scholar 

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Correspondence to Satoshi Yokose.

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This work was supported in part by grants-in-aid from the Ministry of Science, Education, and Culture of Japan

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Yokose, S., Kadokura, H., Tajima, N. et al. Platelet-derived growth factor exerts disparate effects on odontoblast differentiation depending on the dimers in rat dental pulp cells. Cell Tissue Res 315, 375–384 (2004). https://doi.org/10.1007/s00441-003-0839-5

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