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Erschienen in: Calcified Tissue International 4/2016

11.06.2016 | Original Research

Sonic Hedgehog Promotes Cementoblastic Differentiation via Activating the BMP Pathways

verfasst von: Won-Jung Bae, Q-Schick Auh, Hyun-Chang Lim, Gyu-Tae Kim, Hyun-Soo Kim, Eun-Cheol Kim

Erschienen in: Calcified Tissue International | Ausgabe 4/2016

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Abstract

Although sonic hedgehog (SHH), an essential molecule in embryogenesis and organogenesis, stimulates proliferation of human periodontal ligament (PDL) stem cells, the effects of recombinant human SHH (rh-SHH) on osteoblastic differentiation are unclear. To reveal the role of SHH in periodontal regeneration, expression of SHH in mouse periodontal tissues and its effects on the osteoblastic/cementoblastic differentiation in human cementoblasts were investigated. SHH is immunolocalized to differentiating cementoblasts, PDL cells, and osteoblasts of the developing mouse periodontium. Addition of rh-SHH increased cell growth, ALP activity, and mineralization nodule formation, and upregulated mRNA expression of osteoblastic and cementoblastic markers. The osteoblastic/cementoblastic differentiation of rh-SHH was abolished by the SHH inhibitor cyclopamine (Cy) and the BMP antagonist noggin. rh-SHH increased the expression of BMP-2 and -4 mRNA, as well as levels of phosphorylated Akt, ERK, p38, and JNK, and of MAPK and NF-κB activation, which were reversed by noggin, Cy, and BMP-2 siRNA. Collectively, this study is the first to demonstrate that SHH can promote cell growth and cell osteoblastic/cementoblastic differentiation via BMP pathway. Thus, SHH plays important roles in the development of periodontal tissue, and might represent a new therapeutic target for periodontitis and periodontal regeneration.
Literatur
1.
Zurück zum Zitat Bartold PM, McCulloch CA, Narayanan AS, Pitaru S (2000) Tissue engineering: a new paradigm for periodontal regeneration based on molecular and cell biology. Periodontology 24:253–269CrossRef Bartold PM, McCulloch CA, Narayanan AS, Pitaru S (2000) Tissue engineering: a new paradigm for periodontal regeneration based on molecular and cell biology. Periodontology 24:253–269CrossRef
2.
Zurück zum Zitat Wang HL, Greenwell H, Fiorellini J, Giannobile W, Offenbacher S, Salkin L, Townsend C, Sheridan P, Genco RJ (2005) Periodontal regeneration. J Periodontol 76(9):1601–1622PubMedCrossRef Wang HL, Greenwell H, Fiorellini J, Giannobile W, Offenbacher S, Salkin L, Townsend C, Sheridan P, Genco RJ (2005) Periodontal regeneration. J Periodontol 76(9):1601–1622PubMedCrossRef
3.
Zurück zum Zitat Menicanin D, Hynes K, Han J, Gronthos S, Bartold PM (2015) Cementum and periodontal ligament regeneration. Adv Exp Med Biol 881:207–236PubMedCrossRef Menicanin D, Hynes K, Han J, Gronthos S, Bartold PM (2015) Cementum and periodontal ligament regeneration. Adv Exp Med Biol 881:207–236PubMedCrossRef
4.
Zurück zum Zitat Foster BL, Somerman MJ (2012) Cementum. In: McCauley LK, Somerman MJ (eds) Mineralized tissues in oral and craniofacial science: biological principles and clinical correlates, 1st edn. Wiley-Blackwell, Ames, pp 169–192 Foster BL, Somerman MJ (2012) Cementum. In: McCauley LK, Somerman MJ (eds) Mineralized tissues in oral and craniofacial science: biological principles and clinical correlates, 1st edn. Wiley-Blackwell, Ames, pp 169–192
5.
Zurück zum Zitat Kitagawa M, Tahara H, Kitagawa S, Oka H, Kudo Y, Sato S, Ogawa I, Miyaichi M, Takata T (2006) Characterization of established cementoblast-like cell lines from human cementum-lining cells in vitro and in vivo. Bone 39(5):1035–1042PubMedCrossRef Kitagawa M, Tahara H, Kitagawa S, Oka H, Kudo Y, Sato S, Ogawa I, Miyaichi M, Takata T (2006) Characterization of established cementoblast-like cell lines from human cementum-lining cells in vitro and in vivo. Bone 39(5):1035–1042PubMedCrossRef
6.
Zurück zum Zitat Lee SI, Lee DW, Yun HM, Cha HJ, Bae CH, Cho ES, Kim EC (2015) Expression of thymosin beta-4 in human periodontal ligament cells and mouse periodontal tissue and its role in osteoblastic/cementoblastic differentiation. Differentiation 90(1–3):16–26PubMedCrossRef Lee SI, Lee DW, Yun HM, Cha HJ, Bae CH, Cho ES, Kim EC (2015) Expression of thymosin beta-4 in human periodontal ligament cells and mouse periodontal tissue and its role in osteoblastic/cementoblastic differentiation. Differentiation 90(1–3):16–26PubMedCrossRef
7.
Zurück zum Zitat Jin H, Choung HW, Lim KT, Jin B, Jin C, Chung JH, Choung PH (2015) Recombinant human plasminogen activator inhibitor-1 promotes cementogenic differentiation of human periodontal ligament stem cells. Tissue Eng Part A 21(23–24):2817–2828PubMedCrossRef Jin H, Choung HW, Lim KT, Jin B, Jin C, Chung JH, Choung PH (2015) Recombinant human plasminogen activator inhibitor-1 promotes cementogenic differentiation of human periodontal ligament stem cells. Tissue Eng Part A 21(23–24):2817–2828PubMedCrossRef
8.
Zurück zum Zitat Hoz L, Romo E, Zeichner-David M, Sanz M, Nuñez J, Gaitán L, Mercado G, Arzate H (2012) Cementum protein 1 (CEMP1) induces differentiation by human periodontal ligament cells under three-dimensional culture conditions. Cell Biol Int 36(2):129–136PubMedCrossRef Hoz L, Romo E, Zeichner-David M, Sanz M, Nuñez J, Gaitán L, Mercado G, Arzate H (2012) Cementum protein 1 (CEMP1) induces differentiation by human periodontal ligament cells under three-dimensional culture conditions. Cell Biol Int 36(2):129–136PubMedCrossRef
9.
Zurück zum Zitat Bosshardt DD, Sculean A, Windisch P, Pjetursson BE, Lang NP (2005) Effects of enamel matrix proteins on tissue formation along the roots of human teeth. J Periodontal Res 40(2):158–167PubMedCrossRef Bosshardt DD, Sculean A, Windisch P, Pjetursson BE, Lang NP (2005) Effects of enamel matrix proteins on tissue formation along the roots of human teeth. J Periodontal Res 40(2):158–167PubMedCrossRef
10.
Zurück zum Zitat Lee SY, Auh QS, Kang SK, Kim HJ, Lee JW, Noh K, Jang JH, Kim EC (2014) Combined effects of dentin sialoprotein and bone morphogenetic protein-2 on differentiation in human cementoblasts. Cell Tissue Res 357(1):119–132PubMedCrossRef Lee SY, Auh QS, Kang SK, Kim HJ, Lee JW, Noh K, Jang JH, Kim EC (2014) Combined effects of dentin sialoprotein and bone morphogenetic protein-2 on differentiation in human cementoblasts. Cell Tissue Res 357(1):119–132PubMedCrossRef
11.
Zurück zum Zitat Ingham PW, McMahon AP (2001) Hedgehog signaling in animal development: paradigms and principles. Genes Dev 15(23):3059–3087PubMedCrossRef Ingham PW, McMahon AP (2001) Hedgehog signaling in animal development: paradigms and principles. Genes Dev 15(23):3059–3087PubMedCrossRef
12.
Zurück zum Zitat Choudhry Z, Rikani AA, Choudhry AM, Tariq S, Zakaria F, Asghar MW, Sarfraz NK, Haider K, Shafiq AA, Mobassarah NJ (2014) Sonic hedgehog signaling pathway: a complex network. Ann Neurosci 21(1):28–31PubMedPubMedCentralCrossRef Choudhry Z, Rikani AA, Choudhry AM, Tariq S, Zakaria F, Asghar MW, Sarfraz NK, Haider K, Shafiq AA, Mobassarah NJ (2014) Sonic hedgehog signaling pathway: a complex network. Ann Neurosci 21(1):28–31PubMedPubMedCentralCrossRef
13.
Zurück zum Zitat Hu X, Huang J, Feng L, Fukudome S, Hamajima Y, Lin J (2010) Sonic hedgehog (SHH) promotes the differentiation of mouse cochlear neural progenitors via the Math1-Brn3.1 signaling pathway in vitro. J Neurosci Res 88(5):927–935PubMedPubMedCentralCrossRef Hu X, Huang J, Feng L, Fukudome S, Hamajima Y, Lin J (2010) Sonic hedgehog (SHH) promotes the differentiation of mouse cochlear neural progenitors via the Math1-Brn3.1 signaling pathway in vitro. J Neurosci Res 88(5):927–935PubMedPubMedCentralCrossRef
14.
Zurück zum Zitat Elia D, Madhala D, Ardon E, Reshef R, Halvey O (2007) Sonic hedgehog promotes proliferation and differentiation of adult muscle cells: involvement of MAPK/ERK and PI3K/Akt pathways. Biochim Biophys Acta 1773(9):1438–1446PubMedCrossRef Elia D, Madhala D, Ardon E, Reshef R, Halvey O (2007) Sonic hedgehog promotes proliferation and differentiation of adult muscle cells: involvement of MAPK/ERK and PI3K/Akt pathways. Biochim Biophys Acta 1773(9):1438–1446PubMedCrossRef
15.
Zurück zum Zitat Dutton R, Yamada T, Turnley A, Bartlett PF, Murphy M (1999) Sonic hedgehog promotes neuronal differentiation of murine spinal cord precursors and collaborates with neurotrophin 3 to induce Islet-1. J Neurosci 19(7):2601–2608PubMed Dutton R, Yamada T, Turnley A, Bartlett PF, Murphy M (1999) Sonic hedgehog promotes neuronal differentiation of murine spinal cord precursors and collaborates with neurotrophin 3 to induce Islet-1. J Neurosci 19(7):2601–2608PubMed
16.
Zurück zum Zitat Warzecha J, Göttig S, Brüning C, Lindhorst E, Arabmothlagh M, Kuth A (2006) Sonic hedgehog protein promotes proliferation and chondrogenic differentiation of bone marrow-derived mesenchymal stem cells in vitro. J Orthop Sci 11(5):491–496PubMedCrossRef Warzecha J, Göttig S, Brüning C, Lindhorst E, Arabmothlagh M, Kuth A (2006) Sonic hedgehog protein promotes proliferation and chondrogenic differentiation of bone marrow-derived mesenchymal stem cells in vitro. J Orthop Sci 11(5):491–496PubMedCrossRef
17.
Zurück zum Zitat Chiang C, Litingtung Y, Lee E, Young KE, Corden JL, Westphal H, Beachy PA (1996) Cyclopia and defective axial patterning in mice lacking sonic hedgehog gene function. Nature 383(6599):407–413PubMedCrossRef Chiang C, Litingtung Y, Lee E, Young KE, Corden JL, Westphal H, Beachy PA (1996) Cyclopia and defective axial patterning in mice lacking sonic hedgehog gene function. Nature 383(6599):407–413PubMedCrossRef
18.
Zurück zum Zitat Miyaji T, Nakase T, Iwasaki M, Kuriyama K, Tamai N, Highchi C, Myoui A, Tomita T, Yoshigawa H (2003) Expression and distribution of transcripts for sonic hedgehog in the early phase of fracture repair. Histochem Cell Biol 119(3):233–237PubMed Miyaji T, Nakase T, Iwasaki M, Kuriyama K, Tamai N, Highchi C, Myoui A, Tomita T, Yoshigawa H (2003) Expression and distribution of transcripts for sonic hedgehog in the early phase of fracture repair. Histochem Cell Biol 119(3):233–237PubMed
19.
Zurück zum Zitat Levi B, James AW, Nelson ER, Li S, Peng M, Commons GW, Lee M, Wu B, Longaker MT (2011) Human adipose-derived stromal cells stimulate autogenous skeletal repair via paracrine Hedgehog signaling with calvarial osteoblasts. Stem Cells Dev 20(2):243–257PubMedCrossRef Levi B, James AW, Nelson ER, Li S, Peng M, Commons GW, Lee M, Wu B, Longaker MT (2011) Human adipose-derived stromal cells stimulate autogenous skeletal repair via paracrine Hedgehog signaling with calvarial osteoblasts. Stem Cells Dev 20(2):243–257PubMedCrossRef
20.
Zurück zum Zitat Gritli-Linde A, Bei M, Maas R, Zhang XM, Linde A, McMahon AP (2002) Shh signaling within the dental epithelium is necessary for cell proliferation, growth and polarization. Development 129(23):5323–5337PubMedCrossRef Gritli-Linde A, Bei M, Maas R, Zhang XM, Linde A, McMahon AP (2002) Shh signaling within the dental epithelium is necessary for cell proliferation, growth and polarization. Development 129(23):5323–5337PubMedCrossRef
21.
Zurück zum Zitat Seidel K, Ahn CP, Lyons D, Nee A, Ting K, Brwonell I, Cao T, Carano RA, Curran T, Schober M, Fuchs E, Joyner A, Marin GR, de Sauvage FJ, Klein OD (2010) Hedgehog signaling regulates the generation of ameloblast progenitors in the continuously growing mouse incisor. Development 137(22):3753–3761PubMedPubMedCentralCrossRef Seidel K, Ahn CP, Lyons D, Nee A, Ting K, Brwonell I, Cao T, Carano RA, Curran T, Schober M, Fuchs E, Joyner A, Marin GR, de Sauvage FJ, Klein OD (2010) Hedgehog signaling regulates the generation of ameloblast progenitors in the continuously growing mouse incisor. Development 137(22):3753–3761PubMedPubMedCentralCrossRef
22.
Zurück zum Zitat Gaspard N, Bouschet T, Hourez R, Dimidschstein J, Naeije G, van den Ameele J, Espuny-Camacho I, Herpoel A, Passante L, Scjiffmann SN, Gaillard A, Vanderhaeghen P (2008) An intrinsic mechanism of corticogenesis from embryonic stem cells. Nature 455(7211):351–357PubMedCrossRef Gaspard N, Bouschet T, Hourez R, Dimidschstein J, Naeije G, van den Ameele J, Espuny-Camacho I, Herpoel A, Passante L, Scjiffmann SN, Gaillard A, Vanderhaeghen P (2008) An intrinsic mechanism of corticogenesis from embryonic stem cells. Nature 455(7211):351–357PubMedCrossRef
23.
Zurück zum Zitat James AW, Leucht P, Levi B, Carre AL, Xu Y, Helms JA, Longaker MT (2010) Sonic Hedgehog influences the balance of osteogenesis and adipogenesis in mouse adipose-derived stromal cells. Tissue Eng Part A 16(8):2605–2616PubMedPubMedCentralCrossRef James AW, Leucht P, Levi B, Carre AL, Xu Y, Helms JA, Longaker MT (2010) Sonic Hedgehog influences the balance of osteogenesis and adipogenesis in mouse adipose-derived stromal cells. Tissue Eng Part A 16(8):2605–2616PubMedPubMedCentralCrossRef
24.
Zurück zum Zitat Spinella-Jaegle S, Rawadi G, Kawai S, Gallea S, Faucheu C, Mollat P, Courtois B, Bergaud B, Ramez V, Blanchet AM, Adelmant G, Baron R, Roman-Roman S (2001) Sonic hedgehog increases the commitment of pluripotent mesenchymal cells into the osteoblastic lineage and abolishes adipocytic differentiation. J Cell Sci 114(Pt 11):2085–2094PubMed Spinella-Jaegle S, Rawadi G, Kawai S, Gallea S, Faucheu C, Mollat P, Courtois B, Bergaud B, Ramez V, Blanchet AM, Adelmant G, Baron R, Roman-Roman S (2001) Sonic hedgehog increases the commitment of pluripotent mesenchymal cells into the osteoblastic lineage and abolishes adipocytic differentiation. J Cell Sci 114(Pt 11):2085–2094PubMed
25.
Zurück zum Zitat Tian Y, Xu Y, Fu Q, Dong Y (2012) Osterix is required for Sonic hedgehog-induced osteoblastic MC3T3-E1 cell differentiation. Cell Biochem Biophys 64(3):169–176PubMedCrossRef Tian Y, Xu Y, Fu Q, Dong Y (2012) Osterix is required for Sonic hedgehog-induced osteoblastic MC3T3-E1 cell differentiation. Cell Biochem Biophys 64(3):169–176PubMedCrossRef
26.
Zurück zum Zitat Ho JE, Chung EH, Wall S, Schaffer DV, Healy KE (2007) Immobilized sonic hedgehog N-terminal signaling domain enhances differentiation of bone marrow-derived mesenchymal stem cells. J Biomed Mater Res A 83(4):1200–1208PubMedCrossRef Ho JE, Chung EH, Wall S, Schaffer DV, Healy KE (2007) Immobilized sonic hedgehog N-terminal signaling domain enhances differentiation of bone marrow-derived mesenchymal stem cells. J Biomed Mater Res A 83(4):1200–1208PubMedCrossRef
27.
Zurück zum Zitat van der Horst G, Farih-Sips H, Löwik CW, Karperien M (2003) Hedgehog stimulates only osteoblastic differentiation of undifferentiated KS483 cells. Bone 33(6):899–910PubMedCrossRef van der Horst G, Farih-Sips H, Löwik CW, Karperien M (2003) Hedgehog stimulates only osteoblastic differentiation of undifferentiated KS483 cells. Bone 33(6):899–910PubMedCrossRef
28.
Zurück zum Zitat Jemtland R, Divieti P, Lee K, Segre GV (2003) Hedgehog promotes primary osteoblast differentiation and increases PTHrP mRNA expression and iPTHrP secretion. Bone 32(6):611–620PubMedCrossRef Jemtland R, Divieti P, Lee K, Segre GV (2003) Hedgehog promotes primary osteoblast differentiation and increases PTHrP mRNA expression and iPTHrP secretion. Bone 32(6):611–620PubMedCrossRef
29.
Zurück zum Zitat Xia L, Zhang M, Chang Q, Wang L, Zeng D, Zhang X, Zhang Z, Jiang X (2013) Enhanced dentin-like mineralized tissue formation by AdShh-transfected human dental pulp cells and porous calcium phosphate cement. PLoS One 8(5):e62645PubMedPubMedCentralCrossRef Xia L, Zhang M, Chang Q, Wang L, Zeng D, Zhang X, Zhang Z, Jiang X (2013) Enhanced dentin-like mineralized tissue formation by AdShh-transfected human dental pulp cells and porous calcium phosphate cement. PLoS One 8(5):e62645PubMedPubMedCentralCrossRef
30.
Zurück zum Zitat Takahashi S, Kawashima N, Sakamoto K, Nakata A, Kameda T, Sugiyama AT, Katsube K, Suda H (2007) Differentiation of an ameloblast-lineage cell line (ALC) is induced by Sonic hedgehog signaling. Biochem Biophys Res Commun 353(2):405–411PubMedCrossRef Takahashi S, Kawashima N, Sakamoto K, Nakata A, Kameda T, Sugiyama AT, Katsube K, Suda H (2007) Differentiation of an ameloblast-lineage cell line (ALC) is induced by Sonic hedgehog signaling. Biochem Biophys Res Commun 353(2):405–411PubMedCrossRef
31.
Zurück zum Zitat Jiang Q, Du J, Yin X, Shan Z, Ma Y, Ma P, Du J, Fan Z (2013) Shh signaling, negatively regulated by BMP signaling, inhibits the osteo/dentinogenic differentiation potentials of mesenchymal stem cells from apical papilla. Mol Cell Biochem 383(1–2):85–93PubMedCrossRef Jiang Q, Du J, Yin X, Shan Z, Ma Y, Ma P, Du J, Fan Z (2013) Shh signaling, negatively regulated by BMP signaling, inhibits the osteo/dentinogenic differentiation potentials of mesenchymal stem cells from apical papilla. Mol Cell Biochem 383(1–2):85–93PubMedCrossRef
32.
Zurück zum Zitat Plaisant M, Fontaine C, Cousin W, Rochet N, Dani C, Peraldi P (2009) Activation of hedgehog signaling inhibits osteoblast differentiation of human mesenchymal stem cells. Stem Cells 27(3):703–713PubMedCrossRef Plaisant M, Fontaine C, Cousin W, Rochet N, Dani C, Peraldi P (2009) Activation of hedgehog signaling inhibits osteoblast differentiation of human mesenchymal stem cells. Stem Cells 27(3):703–713PubMedCrossRef
33.
Zurück zum Zitat Krishnan V, Ma Y, Moseley J, Geiser A, Fraint S, Frolik C (2001) Bone anabolic effects of Sonic/Indian hedgehog are mediated by BMP-2/4-dependent pathways in the neonatal rat metatarsal model. Endocrinology 142(2):940–947PubMedCrossRef Krishnan V, Ma Y, Moseley J, Geiser A, Fraint S, Frolik C (2001) Bone anabolic effects of Sonic/Indian hedgehog are mediated by BMP-2/4-dependent pathways in the neonatal rat metatarsal model. Endocrinology 142(2):940–947PubMedCrossRef
34.
Zurück zum Zitat Spinella-Jaeqle S, Rawadi G, Kawai S, Gallea S, Faucheu C, Mollat P (2001) Sonic hedgehog increases the commitment of pluripotent mesenchymal cells into the osteoblastic lineage and abolishes adipocytic differentiation. J Cell Sci 114(Pt 111):2085–2094 Spinella-Jaeqle S, Rawadi G, Kawai S, Gallea S, Faucheu C, Mollat P (2001) Sonic hedgehog increases the commitment of pluripotent mesenchymal cells into the osteoblastic lineage and abolishes adipocytic differentiation. J Cell Sci 114(Pt 111):2085–2094
35.
Zurück zum Zitat Hammerschmidt M, Brook A, McMahon AJ (1997) The world according to hedgehog. Trends Genet 13(1):14–21PubMedCrossRef Hammerschmidt M, Brook A, McMahon AJ (1997) The world according to hedgehog. Trends Genet 13(1):14–21PubMedCrossRef
36.
Zurück zum Zitat Bitgood MJ, McMahon AP (1995) Hedgehog and Bmp genes are coexpressed at many diverse sites of cell-cell interaction in the mouse embryo. Dev Biol 172(1):126–138PubMedCrossRef Bitgood MJ, McMahon AP (1995) Hedgehog and Bmp genes are coexpressed at many diverse sites of cell-cell interaction in the mouse embryo. Dev Biol 172(1):126–138PubMedCrossRef
37.
Zurück zum Zitat Martínez C, Smith PC, Rodriguez JP, Palma V (2011) Sonic hedgehog stimulates proliferation of human periodontal ligament stem cells. J Dent Res 90(4):483–488PubMedCrossRef Martínez C, Smith PC, Rodriguez JP, Palma V (2011) Sonic hedgehog stimulates proliferation of human periodontal ligament stem cells. J Dent Res 90(4):483–488PubMedCrossRef
38.
Zurück zum Zitat Dassule HR, Lewis P, Bei M, Maas R, McMahon AP (2000) Sonic hedgehog regulates growth and morphogenesis of the tooth. Development 127(22):4775–4785PubMed Dassule HR, Lewis P, Bei M, Maas R, McMahon AP (2000) Sonic hedgehog regulates growth and morphogenesis of the tooth. Development 127(22):4775–4785PubMed
39.
Zurück zum Zitat Wu C, Shimo T, Liu M, Pacifici M, Koyama E (2003) Sonic hedgehog functions as a mitogen during bell stage of odontogenesis. Connect Tissue Res 44(Suppl 1):92–96PubMedCrossRef Wu C, Shimo T, Liu M, Pacifici M, Koyama E (2003) Sonic hedgehog functions as a mitogen during bell stage of odontogenesis. Connect Tissue Res 44(Suppl 1):92–96PubMedCrossRef
40.
Zurück zum Zitat Gulino R, Gulisano M (2013) Noggin and Sonic hedgehog are involved in compensatory changes within the motoneuron-depleted mouse spinal cord. J Neurol Sci 332(1–2):102–109PubMedCrossRef Gulino R, Gulisano M (2013) Noggin and Sonic hedgehog are involved in compensatory changes within the motoneuron-depleted mouse spinal cord. J Neurol Sci 332(1–2):102–109PubMedCrossRef
41.
Zurück zum Zitat van den Brink GR, Hardwick JC, Nielsen C, Xu C, ten Kate FJ, Glickman J, van Deventer SJ, Roberts DJ, Peppelenbosch MP (2002) Sonic hedgehog expression correlates with fundic gland differentiation in the adult gastrointestinal tract. Gut 51(5):628–633PubMedPubMedCentralCrossRef van den Brink GR, Hardwick JC, Nielsen C, Xu C, ten Kate FJ, Glickman J, van Deventer SJ, Roberts DJ, Peppelenbosch MP (2002) Sonic hedgehog expression correlates with fundic gland differentiation in the adult gastrointestinal tract. Gut 51(5):628–633PubMedPubMedCentralCrossRef
42.
Zurück zum Zitat Lai K, Kaspar BK, Gage FH, Schaffer DV (2003) Sonic hedgehog regulates adult neural progenitor proliferation in vitro and in vivo. Nat Neurosci 6(1):21–27PubMedCrossRef Lai K, Kaspar BK, Gage FH, Schaffer DV (2003) Sonic hedgehog regulates adult neural progenitor proliferation in vitro and in vivo. Nat Neurosci 6(1):21–27PubMedCrossRef
43.
Zurück zum Zitat Khan M, Seppala M, Zoupa M, Cobourne MT (2007) Hedgehog pathway gene expression during early development of the molar tooth root in the mouse. Gene Exp Patterns 7(3):239–243CrossRef Khan M, Seppala M, Zoupa M, Cobourne MT (2007) Hedgehog pathway gene expression during early development of the molar tooth root in the mouse. Gene Exp Patterns 7(3):239–243CrossRef
44.
Zurück zum Zitat Ming JE, Roessler E, Muenke M (1998) Human developmental disorders and the Sonic hedgehog pathway. Mol Med Today 4(8):343–349PubMedCrossRef Ming JE, Roessler E, Muenke M (1998) Human developmental disorders and the Sonic hedgehog pathway. Mol Med Today 4(8):343–349PubMedCrossRef
45.
Zurück zum Zitat Nakatomi M, Morita I, Eto K, Ota MS (2006) Sonic hedgehog signaling is important in tooth root development. J Dent Res 85(5):427–431PubMedCrossRef Nakatomi M, Morita I, Eto K, Ota MS (2006) Sonic hedgehog signaling is important in tooth root development. J Dent Res 85(5):427–431PubMedCrossRef
46.
Zurück zum Zitat Nakatomi M, Hovorakova M, Gritli-Linde A, Blair HJ, MacArthur K, Peterka M, Lesot H, Peterkova R, Ruiz-Perez VL, Goodship JA, Peters H (2013) Evc regulates a symmetrical response to Shh signaling in molar development. J Dent Res 92(3):222–228PubMedCrossRef Nakatomi M, Hovorakova M, Gritli-Linde A, Blair HJ, MacArthur K, Peterka M, Lesot H, Peterkova R, Ruiz-Perez VL, Goodship JA, Peters H (2013) Evc regulates a symmetrical response to Shh signaling in molar development. J Dent Res 92(3):222–228PubMedCrossRef
47.
Zurück zum Zitat Alvarez-Pérez MA, Narayanan S, Zeichner-David M, Rodríguez Carmona B, Arzate H (2006) Molecular cloning, expression and immunolocalization of a novel human cementum-derived protein (CP-23). Bone 38(3):409–419PubMedCrossRef Alvarez-Pérez MA, Narayanan S, Zeichner-David M, Rodríguez Carmona B, Arzate H (2006) Molecular cloning, expression and immunolocalization of a novel human cementum-derived protein (CP-23). Bone 38(3):409–419PubMedCrossRef
48.
Zurück zum Zitat Arzate H, Olson SW, Page RC, Narayanan AS (1992) Isolation of human tumor cells that produce cementum proteins in culture. Bone Miner 18(1):15–30PubMedCrossRef Arzate H, Olson SW, Page RC, Narayanan AS (1992) Isolation of human tumor cells that produce cementum proteins in culture. Bone Miner 18(1):15–30PubMedCrossRef
49.
Zurück zum Zitat Saito M, Iwase M, Maslan S, Nozaki N, Yamauchi M, Handa K, Takahashi O, Sato S, Kawase T, Teranaka T, Narayanan AS (2001) Expression of cementum-derived attachment protein in bovine tooth germ during cementogenesis. Bone 29(3):242–248PubMedCrossRef Saito M, Iwase M, Maslan S, Nozaki N, Yamauchi M, Handa K, Takahashi O, Sato S, Kawase T, Teranaka T, Narayanan AS (2001) Expression of cementum-derived attachment protein in bovine tooth germ during cementogenesis. Bone 29(3):242–248PubMedCrossRef
50.
Zurück zum Zitat Eipeldauer S, Thomas A, Hoechtl-Lee L, Kecht M, Binder H, Koettstorfer J, Gregori M, Sarahrudi K (2014) Is sonic Hedgehog involved in human fracture healing?—a prospective study on local and systemic concentrations of SHH. PLoS One 9(12):668CrossRef Eipeldauer S, Thomas A, Hoechtl-Lee L, Kecht M, Binder H, Koettstorfer J, Gregori M, Sarahrudi K (2014) Is sonic Hedgehog involved in human fracture healing?—a prospective study on local and systemic concentrations of SHH. PLoS One 9(12):668CrossRef
51.
Zurück zum Zitat Cai JQ, Huang YZ, Chen XH, Xie HL, Zhu HM, Tang L, Yang ZM, Huang YC, Deng L (2012) Sonic hedgehog enhances the proliferation and osteogenic differentiation of bone marrow-derived mesenchymal stem cells. Cell Biol Int 36(4):349–355PubMedCrossRef Cai JQ, Huang YZ, Chen XH, Xie HL, Zhu HM, Tang L, Yang ZM, Huang YC, Deng L (2012) Sonic hedgehog enhances the proliferation and osteogenic differentiation of bone marrow-derived mesenchymal stem cells. Cell Biol Int 36(4):349–355PubMedCrossRef
52.
Zurück zum Zitat Fu JR, Liu WL, Zhou JF, Sun HY, Xu HZ, Luo L, Zhang H, Zhou YF (2006) Sonic hedgehog protein promotes bone marrow-derived endothelial progenitor cell proliferation, migration and VEGF production via PI 3-kinase/Akt signaling pathways. Acta Pharmacol Sin 27(6):685–693PubMedCrossRef Fu JR, Liu WL, Zhou JF, Sun HY, Xu HZ, Luo L, Zhang H, Zhou YF (2006) Sonic hedgehog protein promotes bone marrow-derived endothelial progenitor cell proliferation, migration and VEGF production via PI 3-kinase/Akt signaling pathways. Acta Pharmacol Sin 27(6):685–693PubMedCrossRef
53.
Zurück zum Zitat Luo JD, Hu TP, Wang L, Chen MS, Liu SM, Chen AF (2009) Sonic hedgehog improves delayed wound healing via enhancing cutaneous nitric oxide function in diabetes. Am J Physiol Endocrinol Metab 297(2):E525–E531PubMedPubMedCentralCrossRef Luo JD, Hu TP, Wang L, Chen MS, Liu SM, Chen AF (2009) Sonic hedgehog improves delayed wound healing via enhancing cutaneous nitric oxide function in diabetes. Am J Physiol Endocrinol Metab 297(2):E525–E531PubMedPubMedCentralCrossRef
54.
Zurück zum Zitat Asai J, Takenaka H, Kusano KF, Ii M, Luedemann C, Curry C, Eaton E, Iwakura A, Tsutsumi Y, Hamada H, Kishimoto S, Thorne T, Kishore R, Losordo DW (2006) Topical sonic hedgehog gene therapy accelerates wound healing in diabetes by enhancing endothelial progenitor cell-mediated microvascular remodeling. Circulation 113(20):2413–2424PubMedCrossRef Asai J, Takenaka H, Kusano KF, Ii M, Luedemann C, Curry C, Eaton E, Iwakura A, Tsutsumi Y, Hamada H, Kishimoto S, Thorne T, Kishore R, Losordo DW (2006) Topical sonic hedgehog gene therapy accelerates wound healing in diabetes by enhancing endothelial progenitor cell-mediated microvascular remodeling. Circulation 113(20):2413–2424PubMedCrossRef
55.
Zurück zum Zitat Edwards PC, Ruggiero S, Fantasia J, Burakoff R, Moorji SM, Paric E, Razzano P, Grande DA, Mason JM (2005) Sonic hedgehog gene-enhanced tissue engineering for bone regeneration. Gene Ther 12(1):75–86PubMedCrossRef Edwards PC, Ruggiero S, Fantasia J, Burakoff R, Moorji SM, Paric E, Razzano P, Grande DA, Mason JM (2005) Sonic hedgehog gene-enhanced tissue engineering for bone regeneration. Gene Ther 12(1):75–86PubMedCrossRef
56.
Zurück zum Zitat Chen JK, Taipale J, Cooper MK, Beachy PA (2002) Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened. Genes Dev 16(21):2743–2748PubMedPubMedCentralCrossRef Chen JK, Taipale J, Cooper MK, Beachy PA (2002) Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened. Genes Dev 16(21):2743–2748PubMedPubMedCentralCrossRef
57.
Zurück zum Zitat Yun HM, Park KR, Quang TH, Oh H, Hong JT, Kim YC, Kim EC (2015) 2,4,5-Trimethoxyldalbergiquinol promotes osteoblastic differentiation and mineralization via the BMP and Wnt/β-catenin pathway. Cell Death Dis 6:e1819PubMedPubMedCentralCrossRef Yun HM, Park KR, Quang TH, Oh H, Hong JT, Kim YC, Kim EC (2015) 2,4,5-Trimethoxyldalbergiquinol promotes osteoblastic differentiation and mineralization via the BMP and Wnt/β-catenin pathway. Cell Death Dis 6:e1819PubMedPubMedCentralCrossRef
58.
Zurück zum Zitat Hallahan AR, Pritchard JI, Chandraratna RA, Ellenbogen RG, Geyer JR, Overland RP, Strand AD, Tapscott SJ, Olson JM (2003) BMP-2 mediates retinoid-induced apoptosis in medulloblastoma cells through a paracrine effect. Nat Med 9(8):1033–1038PubMedCrossRef Hallahan AR, Pritchard JI, Chandraratna RA, Ellenbogen RG, Geyer JR, Overland RP, Strand AD, Tapscott SJ, Olson JM (2003) BMP-2 mediates retinoid-induced apoptosis in medulloblastoma cells through a paracrine effect. Nat Med 9(8):1033–1038PubMedCrossRef
59.
Zurück zum Zitat Gazzerro E, Gangji V, Canalis E (1998) Bone morphogenetic proteins induce the expression of noggin, which limits their activity in cultured rat osteoblasts. J Clin Invest 102(12):2106–2114PubMedPubMedCentralCrossRef Gazzerro E, Gangji V, Canalis E (1998) Bone morphogenetic proteins induce the expression of noggin, which limits their activity in cultured rat osteoblasts. J Clin Invest 102(12):2106–2114PubMedPubMedCentralCrossRef
60.
Zurück zum Zitat Devlin RD, Du Z, Pereira RC, Kimble RB, Economides AN, Jorgetti V, Canalis E (2003) Skeletal overexpression of noggin results in osteopenia and reduced bone formation. Endocrinology 144(5):1972–1978PubMedCrossRef Devlin RD, Du Z, Pereira RC, Kimble RB, Economides AN, Jorgetti V, Canalis E (2003) Skeletal overexpression of noggin results in osteopenia and reduced bone formation. Endocrinology 144(5):1972–1978PubMedCrossRef
61.
Zurück zum Zitat Xiao G, Gopalakrishnan R, Jiang D, Reith E, Benson M, Franceschi RT (2002) Bone morphogenetic proteins, extracellular matrix, and mitogen-activated protein kinase signaling pathways are required for osteoblast-specific gene expression and differentiation in MC3T3-E1 cells. J Bone Miner Res 17(1):101–110PubMedCrossRef Xiao G, Gopalakrishnan R, Jiang D, Reith E, Benson M, Franceschi RT (2002) Bone morphogenetic proteins, extracellular matrix, and mitogen-activated protein kinase signaling pathways are required for osteoblast-specific gene expression and differentiation in MC3T3-E1 cells. J Bone Miner Res 17(1):101–110PubMedCrossRef
62.
Zurück zum Zitat Ghosh-Choudhury N, Mandal CC, Choudhury GG (2007) Statin-induced Ras activation integrates the phosphatidylinositol 3-kinase signal to Akt and MAPK for bone morphogenetic protein-2 expression in osteoblast differentiation. J Biol Chem 282(7):4983–4993PubMedCrossRef Ghosh-Choudhury N, Mandal CC, Choudhury GG (2007) Statin-induced Ras activation integrates the phosphatidylinositol 3-kinase signal to Akt and MAPK for bone morphogenetic protein-2 expression in osteoblast differentiation. J Biol Chem 282(7):4983–4993PubMedCrossRef
63.
Zurück zum Zitat Dormoy V, Danilin S, Lindner V, Thomas L, Rothhut S, Coquard C, Helwig JJ, Jacqmin D, Lang H, Massfelder T (2009) The sonic hedgehog signaling pathway is reactivated in human renal cell carcinoma and plays orchestral role in tumor growth. Mol Cancer 16(8):123CrossRef Dormoy V, Danilin S, Lindner V, Thomas L, Rothhut S, Coquard C, Helwig JJ, Jacqmin D, Lang H, Massfelder T (2009) The sonic hedgehog signaling pathway is reactivated in human renal cell carcinoma and plays orchestral role in tumor growth. Mol Cancer 16(8):123CrossRef
Metadaten
Titel
Sonic Hedgehog Promotes Cementoblastic Differentiation via Activating the BMP Pathways
verfasst von
Won-Jung Bae
Q-Schick Auh
Hyun-Chang Lim
Gyu-Tae Kim
Hyun-Soo Kim
Eun-Cheol Kim
Publikationsdatum
11.06.2016
Verlag
Springer US
Erschienen in
Calcified Tissue International / Ausgabe 4/2016
Print ISSN: 0171-967X
Elektronische ISSN: 1432-0827
DOI
https://doi.org/10.1007/s00223-016-0155-1

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