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The effect of five proteins on stem cells used for osteoblast differentiation and proliferation: a current review of the literature

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Abstract

Bone-tissue engineering is a therapeutic target in the field of dental implant and orthopedic surgery. It is therefore essential to find a microenvironment that enhances the growth and differentiation of osteoblasts both from mesenchymal stem cells (MSCs) and those derived from dental pulp. The aim of this review is to determine the relationship among the proteins fibronectin (FN), osteopontin (OPN), tenascin (TN), bone sialoprotein (BSP), and bone morphogenetic protein (BMP2) and their ability to coat different types of biomaterials and surfaces to enhance osteoblast differentiation. Pre-treatment of biomaterials with FN during the initial phase of osteogenic differentiation on all types of surfaces, including slotted titanium and polymers, provides an ideal microenvironment that enhances adhesion, morphology, and proliferation of pluripotent and multipotent cells. Likewise, in the second stage of differentiation, surface coating with BMP2 decreases the diameter and the pore size of the scaffold, causing better adhesion and reduced proliferation of BMP-MSCs. Coating oligomerization surfaces with OPN and BSP promotes cell adhesion, but it is clear that the polymeric coating material BSP alone is insufficient to induce priming of MSCs and functional osteoblastic differentiation in vivo. Finally, TN is involved in mineralization and can accelerate new bone formation in a multicellular environment but has no effect on the initial stage of osteogenesis.

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Abbreviations

BMSCs:

Bone marrow stromal cells

CaP:

Calcium phosphate

ESCs:

Embryonic stem cells

ECM:

Extracellular matrix

FN:

Fibronectin

HA:

Hydroxyapatite

MSCs:

Mesenchymal stem cells

PEA:

Poly(ethyl acrylate)

PLLA:

Poly(l-lactic acid)

TG:

Tissue transglutaminase

ADSCs:

Adipose-derived stromal cells

ASCs:

Adult human adipose-derived stem cells

ALP:

Alkaline phosphatase

BMPs:

Bone morphogenetic proteins

FGF:

Fibroblast growth factor

HGF:

Hepatocyte growth factor

JNK:

c-Jun NH2-terminal kinase

MMP:

Metalloproteinase

OA:

Osteoactivin

OC:

Osteocalcin

PEMF:

Pulsed electromagnetic fields

PDGF-AB:

Platelet-derived growth factor-AB

PKA:

cAMP-dependent protein kinase

PLGA:

Poly(lactic-co-glycolic acid)

PTH:

Parathyroid hormone

ROK:

Rho-associated protein kinase

TGF-beta1:

Transforming growth factor-beta1

VEGF:

Vascular endothelial growth factor

BSP:

Bone sialoprotein

ERRalpha:

Estrogen receptor-related receptor alpha

GM-CSF:

Granulocyte macrophage colony-stimulating factor

OPN:

Osteopontin

BMSC:

Bone mesenchymal stem cell

AP1:

Activator protein 1

CRE:

cAMP response element

FGF2:

Fibroblast growth factor 2

FRE:

Fibroblast growth factor 2 response element

FSK:

Forskolin

HOX:

Homeodomain protein-binding site

LPS:

Lipopolysaccharide

PDGF:

Platelet-derived growth factor

PCL/pHEMA:

Polycaprolactone/poly(2-hydroxyethyl methacrylate

References

  1. Wilson-Hench J (1987) Osteoinduction. In progress in biomedical engineering. In: Williams DF (ed) Definitions in biomaterials, vol 4. Elsevier, Amsterdam, p 29

    Google Scholar 

  2. Schlegel KA, Fichtner G, Schultze-Mosgau S, Wiltfang J (2003) Histologic findings in sinus augmentation with autogenous bone chips versus a bovine bone substitute. Int J Oral Maxillofac Implants 18(1):53–58

    PubMed  Google Scholar 

  3. Yildirim M, Spiekermann H, Handt S, Edelhoff D (2001) Maxillary sinus augmentation with the xenograft Bio-Oss and autogenous intraoral bone for qualitative improvement of the implant site: a histologic and histomorphometric clinical study in humans. Int J Oral Maxillofac Implants 16(1):23–33

    CAS  PubMed  Google Scholar 

  4. Schimming R, Schmelzeisen R (2004) Tissue-engineered bone for maxillary sinus augmentation. J Oral Maxillofac Surg 62(6):724–729

    PubMed  Google Scholar 

  5. Frohlich M, Grayson WL, Wan LQ, Marolt D, Drobnic M, Vunjak-Novakovic G (2008) Tissue engineered bone grafts: biological requirements, tissue culture and clinical relevance. Curr Stem Cell Res Ther 3(4):254–264

    CAS  PubMed Central  PubMed  Google Scholar 

  6. Mackie EJ, Ramsey S (1996) Modulation of osteoblast behaviour by tenascin. J Cell Sci 109(Pt 6):1597–1604

    CAS  PubMed  Google Scholar 

  7. Neuss S, Becher E, Woltje M, Tietze L, Jahnen-Dechent W (2004) Functional expression of HGF and HGF receptor/c-met in adult human mesenchymal stem cells suggests a role in cell mobilization, tissue repair, and wound healing. Stem Cells 22(3):405–414

    CAS  PubMed  Google Scholar 

  8. Prockop DJ (1997) Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 276(5309):71–74

    CAS  PubMed  Google Scholar 

  9. Mori G, Centonze M, Brunetti G, Ballini A, Oranger A, Mori C et al (2010) Osteogenic properties of human dental pulp stem cells. J Biol Regul Homeost Agents 24(2):167–175

    CAS  PubMed  Google Scholar 

  10. Graziano A, d’Aquino R, Laino G, Papaccio G (2008) Dental pulp stem cells: a promising tool for bone regeneration. Stem Cell Rev 4(1):21–26

    PubMed  Google Scholar 

  11. Cooke MJ, Phillips SR, Shah DS, Athey D, Lakey JH, Przyborski SA (2008) Enhanced cell attachment using a novel cell culture surface presenting functional domains from extracellular matrix proteins. Cytotechnology 56(2):71–79

    CAS  PubMed Central  PubMed  Google Scholar 

  12. Foster LJ, Zeemann PA, Li C, Mann M, Jensen ON, Kassem M (2005) Differential expression profiling of membrane proteins by quantitative proteomics in a human mesenchymal stem cell line undergoing osteoblast differentiation. Stem Cells 23(9):1367–1377

    CAS  PubMed  Google Scholar 

  13. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284(5411):143–147

    CAS  PubMed  Google Scholar 

  14. Gronthos S, Zannettino AC, Hay SJ, Shi S, Graves SE, Kortesidis A et al (2003) Molecular and cellular characterisation of highly purified stromal stem cells derived from human bone marrow. J Cell Sci 116(Pt 9):1827–1835

    CAS  PubMed  Google Scholar 

  15. Salasznyk RM, Williams WA, Boskey A, Batorsky A, Plopper GE (2004) Adhesion to vitronectin and collagen I promotes osteogenic differentiation of human mesenchymal stem cells. J Biomed Biotechnol 2004(1):24–34

    PubMed Central  PubMed  Google Scholar 

  16. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8(4):315–317

    CAS  PubMed  Google Scholar 

  17. Mimura S, Kimura N, Hirata M, Tateyama D, Hayashida M, Umezawa A et al (2011) Growth factor-defined culture medium for human mesenchymal stem cells. Int J Dev Biol 55(2):181–187

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  19. Laino G, d’Aquino R, Graziano A, Lanza V, Carinci F, Naro F et al (2005) A new population of human adult dental pulp stem cells: a useful source of living autologous fibrous bone tissue (LAB). J Bone Miner Res 20(8):1394–1402

    PubMed  Google Scholar 

  20. Zhang W, Walboomers XF, van Osch GJ, van den Dolder J, Jansen JA (2008) Hard tissue formation in a porous HA/TCP ceramic scaffold loaded with stromal cells derived from dental pulp and bone marrow. Tissue Eng Part A 14(2):285–294

    PubMed  Google Scholar 

  21. d’Aquino R, Graziano A, Sampaolesi M, Laino G, Pirozzi G, De Rosa A et al (2007) Human postnatal dental pulp cells co-differentiate into osteoblasts and endotheliocytes: a pivotal synergy leading to adult bone tissue formation. Cell Death Differ 14(6):1162–1171

    PubMed  Google Scholar 

  22. Graziano A, d’Aquino R, Laino G, Proto A, Giuliano MT, Pirozzi G et al (2008) Human CD34+ stem cells produce bone nodules in vivo. Cell Prolif 41(1):1–11

    CAS  PubMed  Google Scholar 

  23. Palmieri A, Pezzetti F, Graziano A, Riccardo D, Zollino I, Brunelli G et al (2008) Comparison between osteoblasts derived from human dental pulp stem cells and osteosarcoma cell lines. Cell Biol Int 32(7):733–738

    CAS  PubMed  Google Scholar 

  24. Koyama N, Okubo Y, Nakao K, Bessho K (2009) Evaluation of pluripotency in human dental pulp cells. J Oral Maxillofac Surg 67(3):501–506

    PubMed  Google Scholar 

  25. Laino G, Graziano A, d’Aquino R, Pirozzi G, Lanza V, Valiante S et al (2006) An approachable human adult stem cell source for hard-tissue engineering. J Cell Physiol 206(3):693–701

    CAS  PubMed  Google Scholar 

  26. Galler KM, Cavender A, Yuwono V, Dong H, Shi S, Schmalz G et al (2008) Self-assembling peptide amphiphile nanofibers as a scaffold for dental stem cells. Tissue Eng Part A 14(12):2051–2058

    CAS  PubMed  Google Scholar 

  27. Muthna D, Soukup T, Vavrova J, Mokry J, Cmielova J, Visek B et al (2010) Irradiation of adult human dental pulp stem cells provokes activation of p53, cell cycle arrest, and senescence but not apoptosis. Stem Cells Dev 19(12):1855–1862

    CAS  PubMed  Google Scholar 

  28. Yang X, van der Kraan PM, Bian Z, Fan M, Walboomers XF, Jansen JA (2009) Mineralized tissue formation by BMP2-transfected pulp stem cells. J Dent Res 88(11):1020–1025

    CAS  PubMed  Google Scholar 

  29. Yang X, Walboomers XF, van den Beucken JJ, Bian Z, Fan M, Jansen JA (2009) Hard tissue formation of STRO-1-selected rat dental pulp stem cells in vivo. Tissue Eng Part A 15(2):367–375

    CAS  PubMed  Google Scholar 

  30. Yu J, He H, Tang C, Zhang G, Li Y, Wang R et al (2010) Differentiation potential of STRO-1+ dental pulp stem cells changes during cell passaging. BMC Cell Biol 11:32

    PubMed Central  PubMed  Google Scholar 

  31. Abukawa H, Zhang W, Young CS, Asrican R, Vacanti JP, Kaban LB et al (2009) Reconstructing mandibular defects using autologous tissue-engineered tooth and bone constructs. J Oral Maxillofac Surg 67(2):335–347

    PubMed  Google Scholar 

  32. Graziano A, d’Aquino R, Cusella-De Angelis MG, Laino G, Piattelli A, Pacifici M et al (2007) Concave pit-containing scaffold surfaces improve stem cell-derived osteoblast performance and lead to significant bone tissue formation. PLoS One 2(6):e496

    PubMed Central  PubMed  Google Scholar 

  33. Kumabe S, Nakatsuka M, Kim GS, Jue SS, Aikawa F, Shin JW et al (2006) Human dental pulp cell culture and cell transplantation with an alginate scaffold. Okajimas Folia Anat Jpn 82(4):147–155

    CAS  PubMed  Google Scholar 

  34. Otaki S, Ueshima S, Shiraishi K, Sugiyama K, Hamada S, Yorimoto M et al (2007) Mesenchymal progenitor cells in adult human dental pulp and their ability to form bone when transplanted into immunocompromised mice. Cell Biol Int 31(10):1191–1197

    CAS  PubMed  Google Scholar 

  35. Balic A, Aguila HL, Caimano MJ, Francone VP, Mina M (2010) Characterization of stem and progenitor cells in the dental pulp of erupted and unerupted murine molars. Bone 46(6):1639–1651

    PubMed Central  PubMed  Google Scholar 

  36. Tomic S, Djokic J, Vasilijic S, Vucevic D, Todorovic V, Supic G et al (2011) Immunomodulatory properties of mesenchymal stem cells derived from dental pulp and dental follicle are susceptible to activation by Toll-like receptor agonists. Stem Cells Dev 20(4):695–708

    CAS  PubMed  Google Scholar 

  37. Yamada Y, Ito K, Nakamura S, Ueda M, Nagasaka T (2011) Promising cell-based therapy for bone regeneration using stem cells from deciduous teeth, dental pulp, and bone marrow. Cell Transpl 20(7):1003–1013

    Google Scholar 

  38. Lee SH, Ryu JS, Lee JW, Kwak DH, Ko K, Choo YK (2010) Comparison of ganglioside expression between human adipose- and dental pulp-derived stem cell differentiation into osteoblasts. Arch Pharm Res 33(4):585–591

    CAS  PubMed  Google Scholar 

  39. d’Aquino R, De Rosa A, Lanza V, Tirino V, Laino L, Graziano A et al (2009) Human mandible bone defect repair by the grafting of dental pulp stem/progenitor cells and collagen sponge biocomplexes. Eur Cell Mater 18:75–83

    PubMed  Google Scholar 

  40. Riccio M, Resca E, Maraldi T, Pisciotta A, Ferrari A, Bruzzesi G et al (2010) Human dental pulp stem cells produce mineralized matrix in 2D and 3D cultures. Eur J Histochem 54(4):e46

    CAS  PubMed Central  PubMed  Google Scholar 

  41. Morito A, Kida Y, Suzuki K, Inoue K, Kuroda N, Gomi K et al (2009) Effects of basic fibroblast growth factor on the development of the stem cell properties of human dental pulp cells. Arch Histol Cytol 72(1):51–64

    CAS  PubMed  Google Scholar 

  42. Mangano C, Paino F, d’Aquino R, De Rosa A, Iezzi G, Piattelli A et al (2011) Human dental pulp stem cells hook into biocoral scaffold forming an engineered biocomplex. PLoS One 6(4):e18721

    CAS  PubMed Central  PubMed  Google Scholar 

  43. Galler KM, Cavender AC, Koeklue U, Suggs LJ, Schmalz G, D’Souza RN (2011) Bioengineering of dental stem cells in a PEGylated fibrin gel. Regen Med 6(2):191–200

    CAS  PubMed  Google Scholar 

  44. Liu HC, LL E, Wang D, Su F, Wu X, Shi ZP et al (2011) Reconstruction of alveolar bone defects using bone morphogenetic protein 2 mediated rabbit dental pulp stem cells seeded on nano-hydroxyapatite/collagen/poly(l-lactide). Tissue Eng Part A 17(19–20):2417–2433

    CAS  PubMed  Google Scholar 

  45. Mangano C, De Rosa A, Desiderio V, d’Aquino R, Piattelli A, De Francesco F et al (2010) The osteoblastic differentiation of dental pulp stem cells and bone formation on different titanium surface textures. Biomaterials 31(13):3543–3551

    CAS  PubMed  Google Scholar 

  46. Huang CH, Tseng WY, Yao CC, Jeng JH, Young TH, Chen YJ (2010) Glucosamine promotes osteogenic differentiation of dental pulp stem cells through modulating the level of the transforming growth factor-beta type I receptor. J Cell Physiol 225(1):140–151

    CAS  PubMed  Google Scholar 

  47. D’ Alimonte I, Nargi E, Mastrangelo F, Falco G, Lanuti P, Marchisio M et al (2011) Vascular endothelial growth factor enhances in vitro proliferation and osteogenic differentiation of human dental pulp stem cells. J Biol Regul Homeost Agents 25(1):57–69

    Google Scholar 

  48. De Rosa A, Tirino V, Paino F, Tartaglione A, Mitsiadis T, Feki A et al (2011) Amniotic fluid-derived mesenchymal stem cells lead to bone differentiation when cocultured with dental pulp stem cells. Tissue Eng Part A 17(5–6):645–653

    PubMed  Google Scholar 

  49. Atari M, Barajas M, Hernandez-Alfaro F, Gil C, Fabregat M, Ferres Padro E et al (2011) Isolation of pluripotent stem cells from human third molar dental pulp. Histol Histopathol 26(8):1057–1070

    CAS  PubMed  Google Scholar 

  50. Atari M, Gil-Recio C, Fabregat M, Garcia-Fernandez D, Barajas M, Carrasco MA et al (2012) Dental pulp of the third molar: a new source of pluripotent-like stem cells. J Cell Sci 125(Pt 14):3343–3356

    CAS  PubMed  Google Scholar 

  51. Pierschbacher MD, Ruoslahti E (1984) Variants of the cell recognition site of fibronectin that retain attachment-promoting activity. Proc Natl Acad Sci USA 81(19):5985–5988

    CAS  PubMed  Google Scholar 

  52. Humphries MJ, Obara M, Olden K, Yamada KM (1989) Role of fibronectin in adhesion, migration, and metastasis. Cancer Invest 7(4):373–393

    CAS  PubMed  Google Scholar 

  53. Ding HT, Wang CG, Zhang TL, Wang K (2006) Fibronectin enhances in vitro vascular calcification by promoting osteoblastic differentiation of vascular smooth muscle cells via ERK pathway. J Cell Biochem 99(5):1343–1352

    CAS  PubMed  Google Scholar 

  54. Kennedy SB, Washburn NR, Simon CG Jr, Amis EJ (2006) Combinatorial screen of the effect of surface energy on fibronectin-mediated osteoblast adhesion, spreading and proliferation. Biomaterials 27(20):3817–3824

    CAS  PubMed  Google Scholar 

  55. Ribeiro N, Sousa SR, Monteiro FJ (2010) Influence of crystallite size of nanophased hydroxyapatite on fibronectin and osteonectin adsorption and on MC3T3-E1 osteoblast adhesion and morphology. J Colloid Interface Sci 351(2):398–406

    CAS  PubMed  Google Scholar 

  56. Rico P, Rodriguez Hernandez JC, Moratal D, Altankov G, Monleon Pradas M, Salmeron-Sanchez M (2009) Substrate-induced assembly of fibronectin into networks: influence of surface chemistry and effect on osteoblast adhesion. Tissue Eng Part A 15(11):3271–3281

    CAS  PubMed  Google Scholar 

  57. Shahryari A, Azari F, Vali H, Omanovic S (2009) The positive influence of electrochemical cyclic potentiodynamic passivation (CPP) of a SS316LS surface on its response to fibronectin and pre-osteoblasts. Phys Chem Chem Phys 11(29):6218–6224

    CAS  PubMed  Google Scholar 

  58. Sasano Y, Li HC, Zhu JX, Imanaka-Yoshida K, Mizoguchi I, Kagayama M (2000) Immunohistochemical localization of type I collagen, fibronectin and tenascin C during embryonic osteogenesis in the dentary of mandibles and tibias in rats. Histochem J 32(10):591–598

    CAS  PubMed  Google Scholar 

  59. Tang CH, Yang RS, Chen YF, Fu WM (2007) Basic fibroblast growth factor stimulates fibronectin expression through phospholipase C gamma, protein kinase C alpha, c-Src, NF-kappaB, and p300 pathway in osteoblasts. J Cell Physiol 211(1):45–55

    CAS  PubMed  Google Scholar 

  60. Ball MD, O’Connor D, Pandit A (2009) Use of tissue transglutaminase and fibronectin to influence osteoblast responses to tricalcium phosphate scaffolds. J Mater Sci Mater Med 20(1):113–122

    CAS  PubMed  Google Scholar 

  61. Forsprecher J, Wang Z, Nelea V, Kaartinen MT (2009) Enhanced osteoblast adhesion on transglutaminase 2-crosslinked fibronectin. Amino Acids 36(4):747–753

    CAS  PubMed  Google Scholar 

  62. Woo DG, Shim MS, Park JS, Yang HN, Lee DR, Park KH (2009) The effect of electrical stimulation on the differentiation of hESCs adhered onto fibronectin-coated gold nanoparticles. Biomaterials 30(29):5631–5638

    CAS  PubMed  Google Scholar 

  63. Wang Z, Telci D, Griffin M (2011) Importance of syndecan-4 and syndecan -2 in osteoblast cell adhesion and survival mediated by a tissue transglutaminase-fibronectin complex. Exp Cell Res 317(3):367–381

    CAS  PubMed  Google Scholar 

  64. Bentmann A, Kawelke N, Moss D, Zentgraf H, Bala Y, Berger I et al (2010) Circulating fibronectin affects bone matrix, whereas osteoblast fibronectin modulates osteoblast function. J Bone Miner Res 25(4):706–715

    CAS  PubMed  Google Scholar 

  65. Cairns ML, Meenan BJ, Burke GA, Boyd AR (2010) Influence of surface topography on osteoblast response to fibronectin coated calcium phosphate thin films. Colloids Surf B Biointerfaces 78(2):283–290

    CAS  PubMed  Google Scholar 

  66. Gonzalez-Garcia C, Sousa SR, Moratal D, Rico P, Salmeron-Sanchez M (2010) Effect of nanoscale topography on fibronectin adsorption, focal adhesion size and matrix organisation. Colloids Surf B Biointerfaces 77(2):181–190

    CAS  PubMed  Google Scholar 

  67. Toworfe GK, Bhattacharyya S, Composto RJ, Adams CS, Shapiro IM, Ducheyne P (2009) Effect of functional end groups of silane self-assembled monolayer surfaces on apatite formation, fibronectin adsorption and osteoblast cell function. J Tissue Eng Regen Med 3(1):26–36

    CAS  PubMed Central  PubMed  Google Scholar 

  68. Tsai WB, Ting YC, Yang JY, Lai JY, Liu HL (2009) Fibronectin modulates the morphology of osteoblast-like cells (MG-63) on nano-grooved substrates. J Mater Sci Mater Med 20(6):1367–1378

    CAS  PubMed  Google Scholar 

  69. Deligianni D, Korovessis P, Porte-Derrieu MC, Amedee J, Repantis T (2006) Experimental usage of hydroxyapatite preadsorption with fibronectin to increase permanent stability and longevity of spinal implants. Stud Health Technol Inform 123:289–298

    PubMed  Google Scholar 

  70. Pegueroles M, Aparicio C, Bosio M, Engel E, Gil FJ, Planell JA et al (2010) Spatial organization of osteoblast fibronectin matrix on titanium surfaces: effects of roughness, chemical heterogeneity and surface energy. Acta Biomater 6(1):291–301

    CAS  PubMed  Google Scholar 

  71. Elias CN, Gravina PA, Silva Filho CE, Nascente PA (2012) Preparation of bioactive titanium surfaces via fluoride and fibronectin retention. Int J Biomater 2012:290179

    PubMed Central  PubMed  Google Scholar 

  72. Rapuano BE, Hackshaw KM, Schniepp HC, MacDonald DE (2012) Effects of coating a titanium alloy with fibronectin on the expression of osteoblast gene markers in the MC3T3 osteoprogenitor cell line. Int J Oral Maxillofac Implants 27(5):1081–1090

    PubMed Central  PubMed  Google Scholar 

  73. Schonmeyr BH, Wong AK, Li S, Gewalli F, Cordiero PG, Mehrara BJ (2008) Treatment of hydroxyapatite scaffolds with fibronectin and fetal calf serum increases osteoblast adhesion and proliferation in vitro. Plast Reconstr Surg 121(3):751–762

    CAS  PubMed  Google Scholar 

  74. Chen C, Lee IS, Zhang SM, Yang HC (2010) Biomimetic apatite formation on calcium phosphate-coated titanium in Dulbecco’s phosphate-buffered saline solution containing CaCl(2) with and without fibronectin. Acta Biomater 6(6):2274–2281

    CAS  PubMed  Google Scholar 

  75. Sogo Y, Ito A, Matsuno T, Oyane A, Tamazawa G, Satoh T et al (2007) Fibronectin-calcium phosphate composite layer on hydroxyapatite to enhance adhesion, cell spread and osteogenic differentiation of human mesenchymal stem cells in vitro. Biomed Mater 2(2):116–123

    CAS  PubMed  Google Scholar 

  76. Sousa SR, Lamghari M, Sampaio P, Moradas-Ferreira P, Barbosa MA (2008) Osteoblast adhesion and morphology on TiO2 depends on the competitive preadsorption of albumin and fibronectin. J Biomed Mater Res A 84(2):281–290

    CAS  PubMed  Google Scholar 

  77. Lehnert M, Gorbahn M, Rosin C, Klein M, Koper I, Al-Nawas B et al (2011) Adsorption and conformation behavior of biotinylated fibronectin on streptavidin-modified TiO(X) surfaces studied by SPR and AFM. Langmuir 27(12):7743–7751

    CAS  PubMed  Google Scholar 

  78. Pugdee K, Shibata Y, Yamamichi N, Tsutsumi H, Yoshinari M, Abiko Y et al (2007) Gene expression of MC3T3-E1 cells on fibronectin-immobilized titanium using tresyl chloride activation technique. Dent Mater J 26(5):647–655

    CAS  PubMed  Google Scholar 

  79. Jimbo R, Sawase T, Shibata Y, Hirata K, Hishikawa Y, Tanaka Y et al (2007) Enhanced osseointegration by the chemotactic activity of plasma fibronectin for cellular fibronectin-positive cells. Biomaterials 28(24):3469–3477

    CAS  PubMed  Google Scholar 

  80. Osathanon T, Bespinyowong K, Arksornnukit M, Takahashi H, Pavasant P (2006) Ti-6Al-7Nb promotes cell spreading and fibronectin and osteopontin synthesis in osteoblast-like cells. J Mater Sci Mater Med 17(7):619–625

    CAS  PubMed  Google Scholar 

  81. Park JM, Koak JY, Jang JH, Han CH, Kim SK, Heo SJ (2006) Osseointegration of anodized titanium implants coated with fibroblast growth factor-fibronectin (FGF-FN) fusion protein. Int J Oral Maxillofac Implants 21(6):859–866

    PubMed  Google Scholar 

  82. Hindie M, Degat MC, Gaudiere F, Gallet O, Van Tassel PR, Pauthe E (2011) Pre-osteoblasts on poly(l-lactic acid) and silicon oxide: influence of fibronectin and albumin adsorption. Acta Biomater 7(1):387–394

    CAS  PubMed  Google Scholar 

  83. Zhang Y, Xiang Q, Dong S, Li C, Zhou Y (2010) Fabrication and characterization of a recombinant fibronectin/cadherin bio-inspired ceramic surface and its influence on adhesion and ossification in vitro. Acta Biomater 6(3):776–785

    CAS  PubMed  Google Scholar 

  84. Muhonen V, Fauveaux C, Olivera G, Vigneron P, Danilov A, Nagel MD et al (2009) Fibronectin modulates osteoblast behavior on Nitinol. J Biomed Mater Res A 88(3):787–796

    CAS  PubMed  Google Scholar 

  85. Susperregui AR, Vinals F, Ho PW, Gillespie MT, Martin TJ, Ventura F (2008) BMP-2 regulation of PTHrP and osteoclastogenic factors during osteoblast differentiation of C2C12 cells. J Cell Physiol 216(1):144–152

    CAS  PubMed  Google Scholar 

  86. Liu H, Zhang R, Chen D, Oyajobi BO, Zhao M (2012) Functional redundancy of type II BMP receptor and type IIB activin receptor in BMP2-induced osteoblast differentiation. J Cell Physiol 227(3):952–963

    CAS  PubMed Central  PubMed  Google Scholar 

  87. Singhatanadgit W, Salih V, Olsen I (2008) RNA interference of the BMPR-IB gene blocks BMP-2-induced osteogenic gene expression in human bone cells. Cell Biol Int 32(11):1362–1370

    CAS  PubMed  Google Scholar 

  88. Ding HF, Liu R, Li BG, Lou JR, Dai KR, Tang TT (2007) Biologic effect and immunoisolating behavior of BMP-2 gene-transfected bone marrow-derived mesenchymal stem cells in APA microcapsules. Biochem Biophys Res Commun 362(4):923–927

    CAS  PubMed  Google Scholar 

  89. Liu R, Ginn SL, Lek M, North KN, Alexander IE, Little DG et al (2009) Myoblast sensitivity and fibroblast insensitivity to osteogenic conversion by BMP-2 correlates with the expression of Bmpr-1a. BMC Musculoskelet Disord 10:51

    PubMed Central  PubMed  Google Scholar 

  90. Gersbach CA, Guldberg RE, Garcia AJ (2007) In vitro and in vivo osteoblastic differentiation of BMP-2- and Runx2-engineered skeletal myoblasts. J Cell Biochem 100(5):1324–1336

    CAS  PubMed  Google Scholar 

  91. Zhao L, Yang S, Zhou GQ, Yang J, Ji D, Sabatakos G et al (2006) Downregulation of cAMP-dependent protein kinase inhibitor gamma is required for BMP-2-induced osteoblastic differentiation. Int J Biochem Cell Biol 38(12):2064–2073

    CAS  PubMed  Google Scholar 

  92. Liu T, Gao Y, Sakamoto K, Minamizato T, Furukawa K, Tsukazaki T et al (2007) BMP-2 promotes differentiation of osteoblasts and chondroblasts in Runx2-deficient cell lines. J Cell Physiol 211(3):728–735

    CAS  PubMed  Google Scholar 

  93. Celil AB, Campbell PG (2005) BMP-2 and insulin-like growth factor-I mediate Osterix (Osx) expression in human mesenchymal stem cells via the MAPK and protein kinase D signaling pathways. J Biol Chem 280(36):31353–31359

    CAS  PubMed  Google Scholar 

  94. Lee MH, Kwon TG, Park HS, Wozney JM, Ryoo HM (2003) BMP-2-induced Osterix expression is mediated by Dlx5 but is independent of Runx2. Biochem Biophys Res Commun 309(3):689–694

    CAS  PubMed  Google Scholar 

  95. Ulsamer A, Ortuno MJ, Ruiz S, Susperregui AR, Osses N, Rosa JL et al (2008) BMP-2 induces Osterix expression through up-regulation of Dlx5 and its phosphorylation by p38. J Biol Chem 283(7):3816–3826

    CAS  PubMed  Google Scholar 

  96. Lavery K, Swain P, Falb D, Alaoui-Ismaili MH (2008) BMP-2/4 and BMP-6/7 differentially utilize cell surface receptors to induce osteoblastic differentiation of human bone marrow-derived mesenchymal stem cells. J Biol Chem 283(30):20948–20958

    CAS  PubMed  Google Scholar 

  97. Zhang M, Yan Y, Lim YB, Tang D, Xie R, Chen A et al (2009) BMP-2 modulates beta-catenin signaling through stimulation of Lrp5 expression and inhibition of beta-TrCP expression in osteoblasts. J Cell Biochem 108(4):896–905

    CAS  PubMed Central  PubMed  Google Scholar 

  98. Jager M, Fischer J, Dohrn W, Li X, Ayers DC, Czibere A et al (2008) Dexamethasone modulates BMP-2 effects on mesenchymal stem cells in vitro. J Orthop Res 26(11):1440–1448

    PubMed  Google Scholar 

  99. Schwartz Z, Simon BJ, Duran MA, Barabino G, Chaudhri R, Boyan BD (2008) Pulsed electromagnetic fields enhance BMP-2 dependent osteoblastic differentiation of human mesenchymal stem cells. J Orthop Res 26(9):1250–1255

    CAS  PubMed  Google Scholar 

  100. Itoh T, Takeda S, Akao Y (2010) MicroRNA-208 modulates BMP-2-stimulated mouse preosteoblast differentiation by directly targeting V-ets erythroblastosis virus E26 oncogene homolog 1. J Biol Chem 285(36):27745–27752

    CAS  PubMed  Google Scholar 

  101. Liu H, Liu Y, Viggeswarapu M, Zheng Z, Titus L, Boden SD (2011) Activation of c-Jun NH(2)-terminal kinase 1 increases cellular responsiveness to BMP-2 and decreases binding of inhibitory Smad6 to the type I BMP receptor. J Bone Miner Res 26(5):1122–1132

    CAS  PubMed  Google Scholar 

  102. Suzuki A, Ghayor C, Guicheux J, Magne D, Quillard S, Kakita A et al (2006) Enhanced expression of the inorganic phosphate transporter Pit-1 is involved in BMP-2-induced matrix mineralization in osteoblast-like cells. J Bone Miner Res 21(5):674–683

    CAS  PubMed  Google Scholar 

  103. Cowan CM, Jiang X, Hsu T, Soo C, Zhang B, Wang JZ et al (2007) Synergistic effects of Nell-1 and BMP-2 on the osteogenic differentiation of myoblasts. J Bone Miner Res 22(6):918–930

    CAS  PubMed Central  PubMed  Google Scholar 

  104. Luppen CA, Chandler RL, Noh T, Mortlock DP, Frenkel B (2008) BMP-2 vs. BMP-4 expression and activity in glucocorticoid-arrested MC3T3-E1 osteoblasts: smad signaling, not alkaline phosphatase activity, predicts rescue of mineralization. Growth Factors 26(4):226–237

    CAS  PubMed Central  PubMed  Google Scholar 

  105. Singh M, Del Carpio-Cano FE, Monroy MA, Popoff SN, Safadi FF (2012) Homeodomain transcription factors regulate BMP-2-induced osteoactivin transcription in osteoblasts. J Cell Physiol 227(1):390–399

    CAS  PubMed  Google Scholar 

  106. Chen PY, Sun JS, Tsuang YH, Chen MH, Weng PW, Lin FH (2010) Simvastatin promotes osteoblast viability and differentiation via Ras/Smad/Erk/BMP-2 signaling pathway. Nutr Res 30(3):191–199

    CAS  PubMed  Google Scholar 

  107. Su JL, Chiou J, Tang CH, Zhao M, Tsai CH, Chen PS et al (2010) CYR61 regulates BMP-2-dependent osteoblast differentiation through the {alpha}v{beta}3 integrin/integrin-linked kinase/ERK pathway. J Biol Chem 285(41):31325–31336

    CAS  PubMed  Google Scholar 

  108. Honda T, Yamamoto H, Ishii A, Inui M (2010) PDZRN3 negatively regulates BMP-2-induced osteoblast differentiation through inhibition of Wnt signaling. Mol Biol Cell 21(18):3269–3277

    CAS  PubMed Central  PubMed  Google Scholar 

  109. Liu X, Zeng B, Zhang C (2011) Osteogenic and angiogenic effects of mesenchymal stromal cells with co-transfected human Ang-1 gene and BMP2 gene. Biotechnol Lett 33(10):1933–1938

    CAS  PubMed  Google Scholar 

  110. Ono M, Inkson CA, Kilts TM, Young MF (2011) WISP-1/CCN4 regulates osteogenesis by enhancing BMP-2 activity. J Bone Miner Res 26(1):193–208

    CAS  PubMed  Google Scholar 

  111. Carpenter RS, Goodrich LR, Frisbie DD, Kisiday JD, Carbone B, McIlwraith CW et al (2010) Osteoblastic differentiation of human and equine adult bone marrow-derived mesenchymal stem cells when BMP-2 or BMP-7 homodimer genetic modification is compared to BMP-2/7 heterodimer genetic modification in the presence and absence of dexamethasone. J Orthop Res 28(10):1330–1337

    CAS  PubMed Central  PubMed  Google Scholar 

  112. Johnson MR, Lee HJ, Bellamkonda RV, Guldberg RE (2009) Sustained release of BMP-2 in a lipid-based microtube vehicle. Acta Biomater 5(1):23–28

    CAS  PubMed Central  PubMed  Google Scholar 

  113. Gutierrez J, Osses N, Brandan E (2006) Changes in secreted and cell associated proteoglycan synthesis during conversion of myoblasts to osteoblasts in response to bone morphogenetic protein-2: role of decorin in cell response to BMP-2. J Cell Physiol 206(1):58–67

    CAS  PubMed  Google Scholar 

  114. Kim IS, Song YM, Cho TH, Kim JY, Weber FE, Hwang SJ (2009) Synergistic action of static stretching and BMP-2 stimulation in the osteoblast differentiation of C2C12 myoblasts. J Biomech 42(16):2721–2727

    PubMed  Google Scholar 

  115. Yang S, Zhao L, Yang J, Chai D, Zhang M, Zhang J et al (2007) deltaEF1 represses BMP-2-induced differentiation of C2C12 myoblasts into the osteoblast lineage. J Biomed Sci 14(5):663–679

    CAS  PubMed  Google Scholar 

  116. Molders M, Felix J, Bingmann D, Hirner A, Wiemann M (2007) Uptake of nickel from 316L stainless steel into contacting osteoblastic cells and metal ion interference with BMP-2-induced alkaline phosphatase. J Biomed Mater Res A 83(2):303–312

    PubMed  Google Scholar 

  117. Minamizato T, Sakamoto K, Liu T, Kokubo H, Katsube K, Perbal B et al (2007) CCN3/NOV inhibits BMP-2-induced osteoblast differentiation by interacting with BMP and Notch signaling pathways. Biochem Biophys Res Commun 354(2):567–573

    CAS  PubMed  Google Scholar 

  118. Kanzaki S, Takahashi T, Kanno T, Ariyoshi W, Shinmyouzu K, Tujisawa T et al (2008) Heparin inhibits BMP-2 osteogenic bioactivity by binding to both BMP-2 and BMP receptor. J Cell Physiol 216(3):844–850

    CAS  PubMed  Google Scholar 

  119. Zanotti S, Smerdel-Ramoya A, Stadmeyer L, Canalis E (2008) Activation of the ERK pathway in osteoblastic cells, role of gremlin and BMP-2. J Cell Biochem 104(4):1421–1426

    CAS  PubMed  Google Scholar 

  120. Verrier S, Meury TR, Kupcsik L, Heini P, Stoll T, Alini M (2010) Platelet-released supernatant induces osteoblastic differentiation of human mesenchymal stem cells: potential role of BMP-2. Eur Cell Mater 20:403–414

    CAS  PubMed  Google Scholar 

  121. Tseng WP, Yang SN, Lai CH, Tang CH (2010) Hypoxia induces BMP-2 expression via ILK, Akt, mTOR, and HIF-1 pathways in osteoblasts. J Cell Physiol 223(3):810–818

    CAS  PubMed  Google Scholar 

  122. Kim HJ, Kim SH (2010) Tanshinone IIA enhances BMP-2-stimulated commitment of C2C12 cells into osteoblasts via p38 activation. Amino Acids 39(5):1217–1226

    CAS  PubMed  Google Scholar 

  123. Takase H, Yano S, Yamaguchi T, Kanazawa I, Hayashi K, Yamamoto M et al (2009) Parathyroid hormone upregulates BMP-2 mRNA expression through mevalonate kinase and Rho kinase inhibition in osteoblastic MC3T3-E1 cells. Horm Metab Res 41(12):861–865

    CAS  PubMed  Google Scholar 

  124. Huang CY, Lee CY, Chen MY, Tsai HC, Hsu HC, Tang CH (2010) Adiponectin increases BMP-2 expression in osteoblasts via AdipoR receptor signaling pathway. J Cell Physiol 224(2):475–483

    CAS  PubMed  Google Scholar 

  125. Mandal CC, Ganapathy S, Gorin Y, Mahadev K, Block K, Abboud HE et al (2010) Reactive oxygen species derived from Nox4 mediate BMP2 gene transcription and osteoblast differentiation. Biochem J 433(2):393–402

    Google Scholar 

  126. Hou CH, Hou SM, Tang CH (2009) Ultrasound increased BMP-2 expression via PI3 K, Akt, c-Fos/c-Jun, and AP-1 pathways in cultured osteoblasts. J Cell Biochem 106(1):7–15

    CAS  PubMed  Google Scholar 

  127. Kim IS, Cho TH, Kim K, Weber FE, Hwang SJ (2010) High power-pulsed Nd:YAG laser as a new stimulus to induce BMP-2 expression in MC3T3-E1 osteoblasts. Lasers Surg Med 42(6):510–518

    PubMed  Google Scholar 

  128. Ishibashi O, Ikegame M, Takizawa F, Yoshizawa T, Moksed MA, Iizawa F et al (2010) 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 222(2):465–473

    CAS  PubMed  Google Scholar 

  129. Ko H, Yang W, Park K, Kim M (2010) Cytotoxicity of mineral trioxide aggregate (MTA) and bone morphogenetic protein 2 (BMP-2) and response of rat pulp to MTA and BMP-2. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 109(6):e103–e108

    PubMed  Google Scholar 

  130. Van der Zande M, Walboomers XF, Briest A, Springer M, Alava JI, Jansen JA (2008) The effect of combined application of TGFbeta-1, BMP-2, and COLLOSS E on the development of bone marrow derived osteoblast-like cells in vitro. J Biomed Mater Res A 86(3):788–795

    PubMed  Google Scholar 

  131. Singhatanadgit W, Salih V, Olsen I (2006) Up-regulation of bone morphogenetic protein receptor IB by growth factors enhances BMP-2-induced human bone cell functions. J Cell Physiol 209(3):912–922

    CAS  PubMed  Google Scholar 

  132. Samee M, Kasugai S, Kondo H, Ohya K, Shimokawa H, Kuroda S (2008) Bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) transfection to human periosteal cells enhances osteoblast differentiation and bone formation. J Pharmacol Sci 108(1):18–31

    CAS  PubMed  Google Scholar 

  133. Kawasaki T, Niki Y, Miyamoto T, Horiuchi K, Matsumoto M, Aizawa M et al (2010) The effect of timing in the administration of hepatocyte growth factor to modulate BMP-2-induced osteoblast differentiation. Biomaterials 31(6):1191–1198

    CAS  PubMed  Google Scholar 

  134. Maegawa N, Kawamura K, Hirose M, Yajima H, Takakura Y, Ohgushi H (2007) Enhancement of osteoblastic differentiation of mesenchymal stromal cells cultured by selective combination of bone morphogenetic protein-2 (BMP-2) and fibroblast growth factor-2 (FGF-2). J Tissue Eng Regen Med 1(4):306–313

    CAS  PubMed  Google Scholar 

  135. Hughes-Fulford M, Li CF (2011) The role of FGF-2 and BMP-2 in regulation of gene induction, cell proliferation and mineralization. J Orthop Surg Res 6(1):8

    PubMed Central  PubMed  Google Scholar 

  136. Kaewsrichan J, Wongwitwichot P, Chandarajoti K, Chua KH, Ruszymah BH (2011) Sequential induction of marrow stromal cells by FGF2 and BMP2 improves their growth and differentiation potential in vivo. Arch Oral Biol 56(1):90–101

    CAS  PubMed  Google Scholar 

  137. Turhani D, Weissenbock M, Stein E, Wanschitz F, Ewers R (2007) Exogenous recombinant human BMP-2 has little initial effects on human osteoblastic cells cultured on collagen type I coated/noncoated hydroxyapatite ceramic granules. J Oral Maxillofac Surg 65(3):485–493

    PubMed  Google Scholar 

  138. Keibl C, Fugl A, Zanoni G, Tangl S, Wolbank S, Redl H et al (2011) Human adipose derived stem cells reduce callus volume upon BMP-2 administration in bone regeneration. Injury 42(8):814–820

    PubMed  Google Scholar 

  139. Lee JW, Kang KS, Lee SH, Kim JY, Lee BK, Cho DW (2011) Bone regeneration using a microstereolithography-produced customized poly(propylene fumarate)/diethyl fumarate photopolymer 3D scaffold incorporating BMP-2 loaded PLGA microspheres. Biomaterials 32(3):744–752

    CAS  PubMed  Google Scholar 

  140. Degat MC, Dubreucq G, Meunier A, Dahri-Correia L, Sedel L, Petite H et al (2009) Enhancement of the biological activity of BMP-2 by synthetic dextran derivatives. J Biomed Mater Res A 88(1):174–183

    PubMed  Google Scholar 

  141. Laflamme C, Rouabhia M (2008) Effect of BMP-2 and BMP-7 homodimers and a mixture of BMP-2/BMP-7 homodimers on osteoblast adhesion and growth following culture on a collagen scaffold. Biomed Mater 3(1):015008

    PubMed  Google Scholar 

  142. Seib FP, Lanfer B, Bornhauser M, Werner C (2010) Biological activity of extracellular matrix-associated BMP-2. J Tissue Eng Regen Med 4(4):324–327

    CAS  PubMed  Google Scholar 

  143. Cowan CM, Aghaloo T, Chou YF, Walder B, Zhang X, Soo C et al (2007) MicroCT evaluation of three-dimensional mineralization in response to BMP-2 doses in vitro and in critical sized rat calvarial defects. Tissue Eng 13(3):501–512

    CAS  PubMed  Google Scholar 

  144. Li H, Dai K, Tang T, Zhang X, Yan M, Lou J (2007) Bone regeneration by implantation of adipose-derived stromal cells expressing BMP-2. Biochem Biophys Res Commun 356(4):836–842

    CAS  PubMed  Google Scholar 

  145. Schofer M, Fuchs-Winkelmann S, Wack C, Rudisile M, Dersch R, Leifeld I et al (2009) Lack of obvious influence of PLLA nanofibers on the gene expression of BMP-2 and VEGF during growth and differentiation of human mesenchymal stem cells. ScientificWorldJournal 9:313–319

    CAS  PubMed  Google Scholar 

  146. Schofer MD, Veltum A, Theisen C, Chen F, Agarwal S, Fuchs-Winkelmann S et al (2011) Functionalisation of PLLA nanofiber scaffolds using a possible cooperative effect between collagen type I and BMP-2: impact on growth and osteogenic differentiation of human mesenchymal stem cells. J Mater Sci Mater Med 22(7):1753–1762

    CAS  PubMed Central  PubMed  Google Scholar 

  147. Schofer MD, Roessler PP, Schaefer J, Theisen C, Schlimme S, Heverhagen JT et al (2011) Electrospun PLLA nanofiber scaffolds and their use in combination with BMP-2 for reconstruction of bone defects. PLoS One 6(9):e25462

    CAS  PubMed Central  PubMed  Google Scholar 

  148. Seol YJ, Park YJ, Lee SC, Kim KH, Lee JY, Kim TI et al (2006) Enhanced osteogenic promotion around dental implants with synthetic binding motif mimicking bone morphogenetic protein (BMP)-2. J Biomed Mater Res A 77(3):599–607

    PubMed  Google Scholar 

  149. Bae SE, Choi J, Joung YK, Park K, Han DK (2012) Controlled release of bone morphogenetic protein (BMP)-2 from nanocomplex incorporated on hydroxyapatite-formed titanium surface. J Control Release 160(3):676–684

    CAS  PubMed  Google Scholar 

  150. Kodama T, Goto T, Miyazaki T, Takahashi T (2008) Bone formation on apatite-coated titanium incorporated with bone morphogenetic protein and heparin. Int J Oral Maxillofac Implants 23(6):1013–1019

    PubMed  Google Scholar 

  151. Kim SE, Song SH, Yu YP, Choi BJ, Kwon IK, Bae MS et al (2011) The effect of immobilization of heparin and bone morphogenic protein-2 (BMP-2) to titanium surfaces on inflammation and osteoblast function. Biomaterials 32(2):366–373

    CAS  PubMed  Google Scholar 

  152. Lee DW, Yun YP, Park K, Kim SE (2012) Gentamicin and bone morphogenic protein-2 (BMP-2)-delivering heparinized-titanium implant with enhanced antibacterial activity and osteointegration. Bone 50(4):974–982

    CAS  PubMed  Google Scholar 

  153. Kim SE, Yun Y-P, Lee JY, Shim J-S, Park K, Huh J-B (2013) Co-delivery of platelet-derived growth factor (PDGF-BB) and bone morphogenic protein (BMP-2) coated onto heparinized titanium for improving osteoblast function and osteointegration. J Tissue Eng Regen Med. doi:10.1002/term.1668

  154. Zhao J, Hu J, Wang S, Sun X, Xia L, Zhang X et al (2010) Combination of beta-TCP and BMP-2 gene-modified bMSCs to heal critical size mandibular defects in rats. Oral Dis 16(1):46–54

    CAS  PubMed  Google Scholar 

  155. Zheng Z, Yin W, Zara JN, Li W, Kwak J, Mamidi R et al (2010) The use of BMP-2 coupled—Nanosilver-PLGA composite grafts to induce bone repair in grossly infected segmental defects. Biomaterials 31(35):9293–9300

    CAS  PubMed Central  PubMed  Google Scholar 

  156. Balmayor ER, Feichtinger GA, Azevedo HS, van Griensven M, Reis RL (2009) Starch-poly-epsilon-caprolactone microparticles reduce the needed amount of BMP-2. Clin Orthop Relat Res 467(12):3138–3148

    CAS  PubMed  Google Scholar 

  157. Chabas D (2005) Osteopontin, a multi-faceted molecule. Med Sci (Paris) 21(10):832–838

    Google Scholar 

  158. Ishijima M, Tsuji K, Rittling SR, Yamashita T, Kurosawa H, Denhardt DT et al (2007) Osteopontin is required for mechanical stress-dependent signals to bone marrow cells. J Endocrinol 193(2):235–243

    CAS  PubMed  Google Scholar 

  159. Li H, Liu Y, Zhang Q, Jing Y, Chen S, Song Z et al (2009) Ras dependent paracrine secretion of osteopontin by Nf1± osteoblasts promote osteoclast activation in a neurofibromatosis type I murine model. Pediatr Res 65(6):613–618

    CAS  PubMed  Google Scholar 

  160. Ono N, Nakashima K, Rittling SR, Schipani E, Hayata T, Soma K et al (2008) Osteopontin negatively regulates parathyroid hormone receptor signaling in osteoblasts. J Biol Chem 283(28):19400–19409

    CAS  PubMed  Google Scholar 

  161. Zirngibl RA, Chan JS, Aubin JE (2008) Estrogen receptor-related receptor alpha (ERRalpha) regulates osteopontin expression through a non-canonical ERRalpha response element in a cell context-dependent manner. J Mol Endocrinol 40(2):61

    CAS  PubMed  Google Scholar 

  162. Liu L, Qin C, Butler WT, Ratner BD, Jiang S (2007) Controlling the orientation of bone osteopontin via its specific binding with collagen I to modulate osteoblast adhesion. J Biomed Mater Res A 80(1):102–110

    PubMed  Google Scholar 

  163. Kato N, Kitahara K, Rittling SR, Nakashima K, Denhardt DT, Kurosawa H et al (2007) Osteopontin deficiency enhances anabolic action of EP4 agonist at a sub-optimal dose in bone. J Endocrinol 193(1):171–182

    CAS  PubMed  Google Scholar 

  164. Addison WN, Masica DL, Gray JJ, McKee MD (2010) Phosphorylation-dependent inhibition of mineralization by osteopontin ASARM peptides is regulated by PHEX cleavage. J Bone Miner Res 25(4):695–705

    CAS  PubMed  Google Scholar 

  165. Wu CC, Huang ST, Lin HC, Tseng TW, Rao QL, Chen MY (2010) Expression of osteopontin and type I collagen of hFOB 1.19 cells on sintered fluoridated hydroxyapatite composite bone graft materials. Implant Dent 19(6):487–497

    PubMed  Google Scholar 

  166. Grimm G, Vila G, Bieglmayer C, Riedl M, Luger A, Clodi M (2010) Changes in osteopontin and in biomarkers of bone turnover during human endotoxemia. Bone 47(2):388–391

    CAS  PubMed  Google Scholar 

  167. Saito K, Nakatomi M, Ida-Yonemochi H, Kenmotsu S, Ohshima H (2011) The expression of GM-CSF and osteopontin in immunocompetent cells precedes the odontoblast differentiation following allogenic tooth transplantation in mice. J Histochem Cytochem 59(5):518–529

    CAS  PubMed  Google Scholar 

  168. Giachelli CM, Steitz S (2000) Osteopontin: a versatile regulator of inflammation and biomineralization. Matrix Biol 19(7):615–622

    CAS  PubMed  Google Scholar 

  169. Suzuki K, Zhu B, Rittling SR, Denhardt DT, Goldberg HA, McCulloch CA et al (2002) Colocalization of intracellular osteopontin with CD44 is associated with migration, cell fusion, and resorption in osteoclasts. J Bone Miner Res 17(8):1486–1497

    CAS  PubMed  Google Scholar 

  170. Bernards MT, Qin C, Jiang S (2008) MC3T3-E1 cell adhesion to hydroxyapatite with adsorbed bone sialoprotein, bone osteopontin, and bovine serum albumin. Colloids Surf B Biointerfaces 64(2):236–247

    CAS  PubMed Central  PubMed  Google Scholar 

  171. Bernards MT, Qin C, Ratner BD, Jiang S (2008) Adhesion of MC3T3-E1 cells to bone sialoprotein and bone osteopontin specifically bound to collagen I. J Biomed Mater Res A 86(3):779–787

    PubMed Central  PubMed  Google Scholar 

  172. Forsprecher J, Wang Z, Goldberg HA, Kaartinen MT (2011) Transglutaminase-mediated oligomerization promotes osteoblast adhesive properties of osteopontin and bone sialoprotein. Cell Adh Migr 5(1):65–72

    PubMed  Google Scholar 

  173. Addison WN, Azari F, Sorensen ES, Kaartinen MT, McKee MD (2007) Pyrophosphate inhibits mineralization of osteoblast cultures by binding to mineral, up-regulating osteopontin, and inhibiting alkaline phosphatase activity. J Biol Chem 282(21):15872–15883

    CAS  PubMed  Google Scholar 

  174. Jensen T, Baas J, Dolathshahi-Pirouz A, Jacobsen T, Singh G, Nygaard JV et al (2011) Osteopontin functionalization of hydroxyapatite nanoparticles in a PDLLA matrix promotes bone formation. J Biomed Mater Res A 99(1):94–101

    CAS  PubMed  Google Scholar 

  175. Chiquet-Ehrismann R, Tucker RP (2004) Connective tissues: signalling by tenascins. Int J Biochem Cell Biol 36(6):1085–1089

    CAS  PubMed  Google Scholar 

  176. Prieto AL, Andersson-Fisone C, Crossin KL (1992) Characterization of multiple adhesive and counteradhesive domains in the extracellular matrix protein cytotactin. J Cell Biol 119(3):663–678

    CAS  PubMed  Google Scholar 

  177. Lotz MM, Burdsal CA, Erickson HP, McClay DR (1989) Cell adhesion to fibronectin and tenascin: quantitative measurements of initial binding and subsequent strengthening response. J Cell Biol 109(4 Pt 1):1795–1805

    CAS  PubMed  Google Scholar 

  178. Roche P, Goldberg HA, Delmas PD, Malaval L (1999) Selective attachment of osteoprogenitors to laminin. Bone 24(4):329–336

    CAS  PubMed  Google Scholar 

  179. Chiquet M, Renedo AS, Huber F, Fluck M (2003) How do fibroblasts translate mechanical signals into changes in extracellular matrix production? Matrix Biol 22(1):73–80

    CAS  PubMed  Google Scholar 

  180. Mackie EJ, Ramsey S (1996) Expression of tenascin in joint-associated tissues during development and postnatal growth. J Anat 188(Pt 1):157–165

    CAS  PubMed  Google Scholar 

  181. Mikura A, Okuhara S, Saito M, Ota M, Ueda K, Iseki S (2009) Association of tenascin-W expression with mineralization in mouse calvarial development. Congenit Anom (Kyoto) 49(2):77–84

    CAS  Google Scholar 

  182. Meloty-Kapella CV, Degen M, Chiquet-Ehrismann R, Tucker RP (2008) Effects of tenascin-W on osteoblasts in vitro. Cell Tissue Res 334(3):445–455

    PubMed  Google Scholar 

  183. Kimura H, Akiyama H, Nakamura T, de Crombrugghe B (2007) Tenascin-W inhibits proliferation and differentiation of preosteoblasts during endochondral bone formation. Biochem Biophys Res Commun 356(4):935–941

    CAS  PubMed  Google Scholar 

  184. Chiquet M, Fambrough DM (1984) Chick myotendinous antigen. I. A monoclonal antibody as a marker for tendon and muscle morphogenesis. J Cell Biol 98(6):1926–1936

    CAS  PubMed  Google Scholar 

  185. Mackie EJ, Murphy LI (1998) The role of tenascin-C and related glycoproteins in early chondrogenesis. Microsc Res Tech 43(2):102–110

    CAS  PubMed  Google Scholar 

  186. Ozcakir-Tomruk C, Chiquet M, Mericske-Stern R (2012) Tenascin-C and matrix metalloproteinase-9 levels in crevicular fluid of teeth and implants. Clin Implant Dent Relat Res 14(5):672–681

    PubMed  Google Scholar 

  187. Juhasz A, Sziklai I, Rakosy Z, Ecsedi S, Adany R, Balazs M (2009) Elevated level of tenascin and matrix metalloproteinase 9 correlates with the bone destruction capacity of cholesteatomas. Otol Neurotol 30(4):559–565

    PubMed  Google Scholar 

  188. Wang J, Zhou HY, Salih E, Xu L, Wunderlich L, Gu X et al (2006) Site-specific in vivo calcification and osteogenesis stimulated by bone sialoprotein. Calcif Tissue Int 79(3):179–189

    CAS  PubMed  Google Scholar 

  189. Wang S, Sasaki Y, Zhou L, Matsumura H, Araki S, Mezawa M et al (2011) Transcriptional regulation of bone sialoprotein gene by interleukin-11. Gene 476(1–2):46–55

    CAS  PubMed  Google Scholar 

  190. Yang Y, Cui Q, Sahai N (2010) How does bone sialoprotein promote the nucleation of hydroxyapatite? A molecular dynamics study using model peptides of different conformations. Langmuir 26(12):9848–9859

    CAS  PubMed  Google Scholar 

  191. Ganss B, Kim RH, Sodek J (1999) Bone sialoprotein. Crit Rev Oral Biol Med 10(1):79–98

    CAS  PubMed  Google Scholar 

  192. Xia B, Wang J, Guo L, Jiang Z (2011) Effect of bone sialoprotein on proliferation and osteodifferentiation of human bone marrow-derived mesenchymal stem cells in vitro. Biologicals 39(4):217–223

    CAS  PubMed  Google Scholar 

  193. Gordon JA, Tye CE, Sampaio AV, Underhill TM, Hunter GK, Goldberg HA (2007) Bone sialoprotein expression enhances osteoblast differentiation and matrix mineralization in vitro. Bone 41(3):462–473

    CAS  PubMed  Google Scholar 

  194. Monfoulet L, Malaval L, Aubin JE, Rittling SR, Gadeau AP, Fricain JC et al (2010) Bone sialoprotein, but not osteopontin, deficiency impairs the mineralization of regenerating bone during cortical defect healing. Bone 46(2):447–452

    CAS  PubMed  Google Scholar 

  195. Gordon JA, Hunter GK, Goldberg HA (2009) Activation of the mitogen-activated protein kinase pathway by bone sialoprotein regulates osteoblast differentiation. Cells Tissues Organs 189(1–4):138–143

    CAS  PubMed  Google Scholar 

  196. Valverde P, Zhang J, Fix A, Zhu J, Ma W, Tu Q et al (2008) Overexpression of bone sialoprotein leads to an uncoupling of bone formation and bone resorption in mice. J Bone Miner Res 23(11):1775–1788

    CAS  PubMed  Google Scholar 

  197. Malaval L, Wade-Gueye NM, Boudiffa M, Fei J, Zirngibl R, Chen F et al (2008) Bone sialoprotein plays a functional role in bone formation and osteoclastogenesis. J Exp Med 205(5):1145–1153

    CAS  PubMed Central  PubMed  Google Scholar 

  198. Malaval L, Monfoulet L, Fabre T, Pothuaud L, Bareille R, Miraux S et al (2009) Absence of bone sialoprotein (BSP) impairs cortical defect repair in mouse long bone. Bone 45(5):853–861

    CAS  PubMed  Google Scholar 

  199. Boudiffa M, Wade-Gueye NM, Guignandon A, Vanden-Bossche A, Sabido O, Aubin JE et al (2010) Bone sialoprotein deficiency impairs osteoclastogenesis and mineral resorption in vitro. J Bone Miner Res 25(12):2669–2679

    PubMed  Google Scholar 

  200. Mezawa M, Araki S, Takai H, Sasaki Y, Wang S, Li X et al (2009) Regulation of human bone sialoprotein gene transcription by platelet-derived growth factor-BB. Gene 435(1–2):80–87

    CAS  PubMed  Google Scholar 

  201. Nakayama Y, Nakajima Y, Kato N, Takai H, Kim DS, Arai M et al (2006) Insulin-like growth factor-I increases bone sialoprotein (BSP) expression through fibroblast growth factor-2 response element and homeodomain protein-binding site in the proximal promoter of the BSP gene. J Cell Physiol 208(2):326–335

    CAS  PubMed  Google Scholar 

  202. Takai H, Araki S, Mezawa M, Kim DS, Li X, Yang L et al (2008) AP1 binding site is another target of FGF2 regulation of bone sialoprotein gene transcription. Gene 410(1):97–104

    CAS  PubMed  Google Scholar 

  203. Wang Z, Li X, Li Z, Yang L, Sasaki Y, Wang S et al (2010) Effects of inorganic polyphosphate on bone sialoprotein gene expression. Gene 452(2):79–86

    CAS  PubMed  Google Scholar 

  204. Yang L, Li Z, Li X, Wang Z, Wang S, Sasaki Y et al (2010) Butyric acid stimulates bone sialoprotein gene transcription. J Oral Sci 52(2):231–237

    CAS  PubMed  Google Scholar 

  205. Yang L, Takai H, Utsunomiya T, Li X, Li Z, Wang Z et al (2010) Kaempferol stimulates bone sialoprotein gene transcription and new bone formation. J Cell Biochem 110(6):1342–1355

    CAS  PubMed  Google Scholar 

  206. Li X, Kato N, Mezawa M, Li Z, Wang Z, Yang L et al (2010) Transcriptional regulation of bone sialoprotein gene by Porphyromonas gingivalis lipopolysaccharide. J Cell Biochem 110(4):823–833

    CAS  PubMed  Google Scholar 

  207. Li Z, Sasaki Y, Mezawa M, Wang S, Li X, Yang L et al (2011) cAMP and fibroblast growth factor 2 regulate bone sialoprotein gene expression in human prostate cancer cells. Gene 471(1–2):1–12

    CAS  PubMed  Google Scholar 

  208. Wang S, Sasaki Y, Ogata Y (2011) Calcium hydroxide regulates bone sialoprotein gene transcription in human osteoblast-like Saos2 cells. J Oral Sci 53(1):77–86

    CAS  PubMed  Google Scholar 

  209. Sasaki Y, Wang S, Ogata Y (2011) Transcriptional regulation of bone sialoprotein gene by CO(2) laser irradiation. J Oral Sci 53(1):51–59

    CAS  PubMed  Google Scholar 

  210. Lamour V, Detry C, Sanchez C, Henrotin Y, Castronovo V, Bellahcene A (2007) Runx2- and histone deacetylase 3-mediated repression is relieved in differentiating human osteoblast cells to allow high bone sialoprotein expression. J Biol Chem 282(50):36240–36249

    CAS  PubMed  Google Scholar 

  211. Nakajima Y, Kato N, Nakayama Y, Kim DS, Takai H, Arai M et al (2006) Effect of chlorpromazine on bone sialoprotein (BSP) gene transcription. J Cell Biochem 97(6):1198–1206

    CAS  PubMed  Google Scholar 

  212. Kato N, Nakayama Y, Nakajima Y, Samoto H, Saito R, Yamanouchi F et al (2006) Regulation of bone sialoprotein (BSP) gene transcription by lipopolysaccharide. J Cell Biochem 97(2):368–379

    CAS  PubMed  Google Scholar 

  213. Karadag A, Fisher LW (2006) Bone sialoprotein enhances migration of bone marrow stromal cells through matrices by bridging MMP-2 to alpha(v)beta3-integrin. J Bone Miner Res 21(10):1627–1636

    CAS  PubMed  Google Scholar 

  214. Chan WD, Goldberg HA, Hunter GK, Dixon SJ, Rizkalla AS (2010) Modification of polymer networks with bone sialoprotein promotes cell attachment and spreading. J Biomed Mater Res A 94(3):945–952

    PubMed  Google Scholar 

  215. Schaeren S, Jaquiery C, Wolf F, Papadimitropoulos A, Barbero A, Schultz-Thater E et al (2010) Effect of bone sialoprotein coating of ceramic and synthetic polymer materials on in vitro osteogenic cell differentiation and in vivo bone formation. J Biomed Mater Res A 92(4):1461–1467

    PubMed  Google Scholar 

  216. Graf HL, Stoeva S, Armbruster FP, Neuhaus J, Hilbig H (2008) Effect of bone sialoprotein and collagen coating on cell attachment to TICER and pure titanium implant surfaces. Int J Oral Maxillofac Surg 37(7):634–640

    PubMed  Google Scholar 

  217. O’Toole GC, Salih E, Gallagher C, FitzPatrick D, O’Higgins N, O’Rourke SK (2004) Bone sialoprotein-coated femoral implants are osteoinductive but mechanically compromised. J Orthop Res 22(3):641–646

    PubMed  Google Scholar 

  218. Hilbig H, Kirsten M, Rupietta R, Graf HL, Thalhammer S, Strasser S, Armbruster FP (2007) Implant surface coatings with bone sialoprotein, collagen, and fibronectin and their effects on cells derived from human maxillar bone. Eur J Med Res 12(1):6–12

    CAS  PubMed  Google Scholar 

  219. Huang GT, Shagramanova K, Chan SW (2007) Formation of odontoblast-like cells from cultured human dental pulp cells on dentin in vitro. J Endod 32(11):1066–1073

    Google Scholar 

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Authors and Affiliations

  1. Laboratory for Regenerative Medicine, College of Dentistry, Universitat Internacional de Catalunya, C/Josep Trueta s/n, Sant Cugat del Vallès, 08195, Barcelona, Spain

    P. Chatakun, R. Núñez-Toldrà, E. J. Díaz López, C. Gil-Recio, E. Martínez-Sarrà, L. Giner-Tarrida & M. Atari

  2. Police General Hospital, Bangkok, Thailand

    P. Chatakun

  3. Chair of Regenerative Implantology MIS-UIC, Universitat Internacional de Catalunya, Barcelona, Spain

    R. Núñez-Toldrà, C. Gil-Recio, E. Martínez-Sarrà, L. Giner-Tarrida & M. Atari

  4. Surgery and Oral Implantology Department, College of Dentistry, Universitat Internacional de Catalunya, Barcelona, Spain

    F. Hernández-Alfaro, E. Ferrés-Padró & M. Atari

  5. Oral and Maxillofacial Surgery Department, Fundacio Hospital de Nens de Barcelona, Barcelona, Spain

    E. Ferrés-Padró

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  1. P. Chatakun
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  2. R. Núñez-Toldrà
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Chatakun, P., Núñez-Toldrà, R., Díaz López, E.J. et al. The effect of five proteins on stem cells used for osteoblast differentiation and proliferation: a current review of the literature. Cell. Mol. Life Sci. 71, 113–142 (2014). https://doi.org/10.1007/s00018-013-1326-0

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  • DOI: https://doi.org/10.1007/s00018-013-1326-0

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