Advertisement

The effects of bısphosphonates on osteonecrosıs of jaw bone: a stem cell perspectıve

  • Hüseyin Abdik
  • Ezgi Avşar Abdik
  • Selami Demirci
  • Ayşegül Doğan
  • Duygu Turan
  • Fikrettin Şahin
Original Article
  • 31 Downloads

Abstract

Bisphosphonate-induced osteonecrosis of the jaw (BIONJ) is a commonly encountered side effect of Bisphosphonates (BPs). Although certain aspects of BIONJ have been studied, the effects of BPs on the proliferation, differentiation, and maintenance of dental stem cells (DSC) in way that might account for development of BIONJ have not been evaluated. In the current study, Dental Pulp Stem Cells (DPSCs), Periodontal Stem Cells (PDLSCs), and human Tooth Germ Stem Cells (hTGSCs) were characterized and then each stem cell type were treated with selected BPs: Zoledronate (ZOL), Alendronate (ALE), and Risedronate (RIS). Negative effect on osteogenesis capacity of DSCs has not been observed after differentiation experiments in vitro. BPs exerted inhibitory effect on the migratory capacities of stem cells confirmed by in vitro scratch assay analysis. Angiogenesis of endothelial cells was blocked by BPs treatment in tube formation analysis. In conclusion, inhibitory effects of BPs on migration capacity of DSCs localized in close proximity to the jaw bone might be the primary reason for the side effects of BPs in the development of BIONJ process. Therefore, further in vivo evidence is required to investigate DSC properties in BP treated animals which might elucidate the importance of DSCs in BIONJ formation.

Keywords

BPs BIONJ DSCs Osteogenesis Migration Angiogenesis 

Notes

Acknowledgements

This study was supported by Yeditepe University. The authors would like to thank Dr. Neslihan Taşlı for her guidance during the experimental stages and Dr. Aslı Hızlı Deniz for her assistance during writing stages.

Compliance with ethical standards

Conflict of interest

The authors deny any conflict of interest.

Supplementary material

11033_2018_4532_MOESM1_ESM.docx (130.6 mb)
Supplementary material 1 (DOCX 133756 KB)

References

  1. 1.
    Blau HM, Brazelton T, Weimann J (2001) The evolving concept of a stem cell: entity or function? Cell 105:829–841CrossRefGoogle Scholar
  2. 2.
    Henningson CT Jr, Stanislaus MA, Gewirtz AM (2003) 28. Embryonic and adult stem cell therapy. J Allergy Clin Immunol 111:S745–S753CrossRefGoogle Scholar
  3. 3.
    Egusa H, Sonoyama W, Nishimura M, Atsuta I, Akiyama K (2012) Stem cells in dentistry–part I: stem cell sources. J Prosthodont Res 56:151–165CrossRefGoogle Scholar
  4. 4.
    Alge DL, Zhou D, Adams LL et al (2010) Donor-matched comparison of dental pulp stem cells and bone marrow-derived mesenchymal stem cells in a rat model. J Tissue Eng Regener Med 4:73–81Google Scholar
  5. 5.
    Ito K, Yamada Y, Nakamura S, Ueda M (2011) Osteogenic potential of effective bone engineering using dental pulp stem cells, bone marrow stem cells, and periosteal cells for osseointegration of dental implants. Int J Oral Maxillofac Implant 26:5Google Scholar
  6. 6.
    Seo B-M, Miura M, Gronthos S et al (2004) Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet 364:149–155CrossRefGoogle Scholar
  7. 7.
    Deal C (2009) Potential new drug targets for osteoporosis. Nat Rev Rheumatol 5:20CrossRefGoogle Scholar
  8. 8.
    Reid D (2011) Handbook of osteoporosis. Springer, BerlinCrossRefGoogle Scholar
  9. 9.
    Hacchou Y, Uematsu T, Ueda O et al (2007) Inorganic polyphosphate: a possible stimulant of bone formation. J Dental Res 86:893–897CrossRefGoogle Scholar
  10. 10.
    Hosseini FS, Soleimanifar F, Khojasteh A, Ardeshirylajimi A (2018) Promoting osteogenic differentiation of human-induced pluripotent stem cells by releasing Wnt/β-catenin signaling activator from the nanofibers. J Cell BiochemGoogle Scholar
  11. 11.
    Rogers M, Frith J, Luckman S et al (1999) Molecular mechanisms of action of bisphosphonates. Bone 24:73S–73S9SCrossRefGoogle Scholar
  12. 12.
    Russell RGG (2007) Bisphosphonates: mode of action and pharmacology. Pediatrics 119:S150–S162CrossRefGoogle Scholar
  13. 13.
    Roelofs AJ, Thompson K, Gordon S, Rogers MJ (2006) Molecular mechanisms of action of bisphosphonates: current status. Clin Cancer Res 12:6222s–6222s30 sCrossRefGoogle Scholar
  14. 14.
    De Ponte FS (2012) Bisphosphonates and osteonecrosis of the jaw: a multidisciplinary approach. Springer, BerlinCrossRefGoogle Scholar
  15. 15.
    Marini F, Brandi ML (2014) Pharmacogenetics of osteoporosis. Best Pract Res Clin Endocrinol Metab, 28, 783–93CrossRefGoogle Scholar
  16. 16.
    Santini D, Vincenzi B, Avvisati G et al (2002) Pamidronate induces modifications of circulating angiogenetic factors in cancer patients. Clin Cancer Res 8:1080–1084Google Scholar
  17. 17.
    Wood J, Bonjean K, Ruetz S et al (2002) Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid. J Pharmacol Exp Ther 302:1055–1061CrossRefGoogle Scholar
  18. 18.
    Ogose A, Motoyama T, Hotta T, Watanabe H (1996) Expression of bone morphogenetic proteins in human osteogenic and epithelial tumor cells. Pathol Int 46:9–14CrossRefPubMedGoogle Scholar
  19. 19.
    Xuan K, Jin F, Liu Y-L et al (2008) Identification of a novel missense mutation of MSX1 gene in Chinese family with autosomal-dominant oligodontia. Arch Oral Biol 53:773–779CrossRefPubMedGoogle Scholar
  20. 20.
    Nam S, Won J-E, Kim C-H, Kim H-W (2011) Odontogenic differentiation of human dental pulp stem cells stimulated by the calcium phosphate porous granules. J Tissue Eng 2011:812547PubMedCentralPubMedGoogle Scholar
  21. 21.
    Doğan A, Yalvaç ME, Şahin F, Kabanov AV, Palotás A, Rizvanov AA (2012) Differentiation of human stem cells is promoted by amphiphilic pluronic block copolymers. Int J Nanomed 7:4849Google Scholar
  22. 22.
    Ding X, Zhou L, Wang J et al (2015) The effects of hierarchical micro/nanosurfaces decorated with TiO2 nanotubes on the bioactivity of titanium implants in vitro and in vivo. Int J Nanomed 10:6955Google Scholar
  23. 23.
    Taşlı PN, Aydın S, Yalvaç ME, Şahin F (2014) Bmp 2 and bmp 7 induce odonto-and osteogenesis of human tooth germ stem cells. Appl Biochem Biotechnol 172:3016–3025CrossRefGoogle Scholar
  24. 24.
    Doğan A, Demirci S, Apdik H, Apdik EA, Şahin F (2017) Dental pulp stem cells (DPSCs) increase prostate cancer cell proliferation and migration under in vitro conditions. Tissue Cell 49:711–718CrossRefGoogle Scholar
  25. 25.
    Lisignoli G, Cristino S, Piacentini A et al (2005) Cellular and molecular events during chondrogenesis of human mesenchymal stromal cells grown in a three-dimensional hyaluronan based scaffold. Biomaterials 26:5677–5686CrossRefGoogle Scholar
  26. 26.
    Woo S-B, Hellstein JW, Kalmar JR (2006) Systematic review: bisphosphonates and osteonecrosis of the jaws. Ann Internal Med 144:753–761CrossRefGoogle Scholar
  27. 27.
    Caplan AI (2007) Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J Cell Physiol 213:341–347CrossRefGoogle Scholar
  28. 28.
    Marchionni C, Bonsi L, Alviano F et al (2009) Angiogenic potential of human dental pulp stromal (stem) cells. Int J Immunopathol Pharmacol 22:699–706CrossRefGoogle Scholar
  29. 29.
    Yu J, Wang Y, Deng Z et al (2007) Odontogenic capability: bone marrow stromal stem cells versus dental pulp stem cells. Biol Cell 99:465–474CrossRefGoogle Scholar
  30. 30.
    Saoji NA (2008) Effect of bisphosphonate on osteogenic differentiation of pulp and PDL Cells. University of Alabama at Birmingham, BirminghamGoogle Scholar
  31. 31.
    Casado-Díaz A, Santiago-Mora R, Dorado G, Quesada-Gómez JM (2013) Risedronate positively affects osteogenic differentiation of human mesenchymal stromal cells. Arch Med Res 44:325–334CrossRefGoogle Scholar
  32. 32.
    Duque G, Rivas D (2007) Alendronate has an anabolic effect on bone through the differentiation of mesenchymal stem cells. J Bone Miner Res 22:1603–1611CrossRefGoogle Scholar
  33. 33.
    von Knoch F, Jaquiery C, Kowalsky M et al (2005) Effects of bisphosphonates on proliferation and osteoblast differentiation of human bone marrow stromal cells. Biomaterials 26:6941–6949CrossRefGoogle Scholar
  34. 34.
    Ruggiero SL (2007) Guidelines for the diagnosis of bisphosphonate-related osteonecrosis of the jaw (BRONJ). Clin Cases Min Bone Metabol 4, 37Google Scholar
  35. 35.
    Zhang Z, Liu W, Zheng Y, Jin L, Yao W, Gao X (2014) SGP-2, an acidic polysaccharide from Sarcandra glabra, inhibits proliferation and migration of human osteosarcoma cells. Food Function 5, 167–75CrossRefGoogle Scholar
  36. 36.
    Pourgonabadi S, Ghorbani A, Mousavi SH (2018) In vitro assessment of alendronate toxic and apoptotic effects on human dental pulp stem cells. Iran J Basic Med Sci 21:905–910Google Scholar
  37. 37.
    Sharma D, Hamlet SM, Petcu EB, Ivanovski S (2016) The effect of bisphosphonates on the endothelial differentiation of mesenchymal stem cells. Sci Rep 6:20580CrossRefPubMedGoogle Scholar
  38. 38.
    Shiomi K, Nagata Y, Kiyono T, Harada A, Hashimoto N (2014) Differential impact of the B isphosphonate A lendronate on undifferentiated and terminally differentiated human myogenic cells. J Pharm Pharmacol 66:418–427CrossRefGoogle Scholar
  39. 39.
    Berrier AL, Yamada KM (2007) Cell–matrix adhesion. J Cell Physiol 213:565–573CrossRefGoogle Scholar
  40. 40.
    Shiba H, Fujita T, Doi N et al (1998) Differential effects of various growth factors and cytokines on the syntheses of DNA, type I collagen, laminin, fibronectin, osteonectin/secreted protein, acidic and rich in cysteine (SPARC), and alkaline phosphatase by human pulp cells in culture. J Cell Physiol 174:194–205CrossRefGoogle Scholar
  41. 41.
    Tabata MJ, Matsumura T, Fujii T, Abe M, Kurisu K (2003) Fibronectin accelerates the growth and differentiation of ameloblast lineage cells in vitro. J Histochem Cytochem 51:1673–1679CrossRefGoogle Scholar
  42. 42.
    Yuasa K, Fukumoto S, Kamasaki Y et al (2004) Laminin α2 is essential for odontoblast differentiation regulating dentin sialoprotein expression. J Biol Chem 279:10286–10292CrossRefGoogle Scholar
  43. 43.
    Yang X, Zhang S, Pang X, Fan M (2012) Retraction: Pro-inflammatory cytokines induce odontogenic differentiation of dental pulp-derived stem cells. J Cell Biochem 113:2796-CrossRefGoogle Scholar
  44. 44.
    Boomsma RA, Geenen DL (2012) Mesenchymal stem cells secrete multiple cytokines that promote angiogenesis and have contrasting effects on chemotaxis and apoptosis. PLoS ONE 7:e35685CrossRefPubMedGoogle Scholar
  45. 45.
    Li Y, Yu X, Lin S, Li X, Zhang S, Song Y-H (2007) Insulin-like growth factor 1 enhances the migratory capacity of mesenchymal stem cells. Biochem Biophys Res Commun 356:780–784CrossRefGoogle Scholar
  46. 46.
    Ponte AL, Marais E, Gallay N et al (2007) The in vitro migration capacity of human bone marrow mesenchymal stem cells: comparison of chemokine and growth factor chemotactic activities. Stem cells 25:1737–1745CrossRefGoogle Scholar
  47. 47.
    Brew K, Nagase H (2010) The tissue inhibitors of metalloproteinases (TIMPs): an ancient family with structural and functional diversity. Biochim Biophys Acta (BBA) 1803:55–71CrossRefGoogle Scholar
  48. 48.
    Ries C, Egea V, Karow M, Kolb H, Jochum M, Neth P (2007) MMP-2, MT1-MMP, and TIMP-2 are essential for the invasive capacity of human mesenchymal stem cells: differential regulation by inflammatory cytokines. Blood 109:4055–4063CrossRefGoogle Scholar
  49. 49.
    Granero-Moltó F, Myers TJ, Weis JA et al (2011) Mesenchymal stem cells expressing insulin-like growth factor-I (MSCIGF) promote fracture healing and restore new bone formation in Irs1 knockout mice: analyses of MSCIGF autocrine and paracrine regenerative effects. Stem Cells 29:1537–1548CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.Department of Genetics and Bioengineering, Faculty of Engineering and ArchitectureYeditepe UniversityIstanbulTurkey
  2. 2.National Heart, Lung, and Blood Institute (NHLBI), NIHBethesdaUSA

Personalised recommendations