[go: up one dir, main page]
Skip to main content

Advertisement

SpringerLink
Log in

The effects of bisphosphonates on osteonecrosis of jaw bone: a stem cell perspective

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Blau HM, Brazelton T, Weimann J (2001) The evolving concept of a stem cell: entity or function? Cell 105:829–841

    Article  CAS  PubMed  Google Scholar 

  2. Henningson CT Jr, Stanislaus MA, Gewirtz AM (2003) 28. Embryonic and adult stem cell therapy. J Allergy Clin Immunol 111:S745–S753

    Article  PubMed  Google Scholar 

  3. Egusa H, Sonoyama W, Nishimura M, Atsuta I, Akiyama K (2012) Stem cells in dentistry–part I: stem cell sources. J Prosthodont Res 56:151–165

    Article  PubMed  Google Scholar 

  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 4:73–81

    CAS  Google Scholar 

  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 26:5

    Google Scholar 

  6. Seo B-M, Miura M, Gronthos S et al (2004) Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet 364:149–155

    Article  CAS  PubMed  Google Scholar 

  7. Deal C (2009) Potential new drug targets for osteoporosis. Nat Rev Rheumatol 5:20

    Article  CAS  Google Scholar 

  8. Reid D (2011) Handbook of osteoporosis. Springer, Berlin

    Book  Google Scholar 

  9. Hacchou Y, Uematsu T, Ueda O et al (2007) Inorganic polyphosphate: a possible stimulant of bone formation. J Dental Res 86:893–897

    Article  CAS  Google Scholar 

  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 Biochem

  11. Rogers M, Frith J, Luckman S et al (1999) Molecular mechanisms of action of bisphosphonates. Bone 24:73S–73S9S

    Article  CAS  PubMed  Google Scholar 

  12. Russell RGG (2007) Bisphosphonates: mode of action and pharmacology. Pediatrics 119:S150–S162

    Article  PubMed  Google Scholar 

  13. Roelofs AJ, Thompson K, Gordon S, Rogers MJ (2006) Molecular mechanisms of action of bisphosphonates: current status. Clin Cancer Res 12:6222s–6222s30 s

    Article  CAS  PubMed  Google Scholar 

  14. De Ponte FS (2012) Bisphosphonates and osteonecrosis of the jaw: a multidisciplinary approach. Springer, Berlin

    Book  Google Scholar 

  15. Marini F, Brandi ML (2014) Pharmacogenetics of osteoporosis. Best Pract Res Clin Endocrinol Metab, 28, 783–93

    Article  CAS  PubMed  Google Scholar 

  16. Santini D, Vincenzi B, Avvisati G et al (2002) Pamidronate induces modifications of circulating angiogenetic factors in cancer patients. Clin Cancer Res 8:1080–1084

    CAS  PubMed  Google Scholar 

  17. Wood J, Bonjean K, Ruetz S et al (2002) Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid. J Pharmacol Exp Ther 302:1055–1061

    Article  CAS  PubMed  Google Scholar 

  18. Ogose A, Motoyama T, Hotta T, Watanabe H (1996) Expression of bone morphogenetic proteins in human osteogenic and epithelial tumor cells. Pathol Int 46:9–14

    Article  CAS  PubMed  Google Scholar 

  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 53:773–779

    Article  CAS  PubMed  Google Scholar 

  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 2011:812547

    PubMed  PubMed Central  Google Scholar 

  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 7:4849

    Google Scholar 

  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 10:6955

    CAS  Google Scholar 

  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 172:3016–3025

    Article  CAS  PubMed  Google Scholar 

  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 49:711–718

    Article  CAS  PubMed  Google Scholar 

  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 26:5677–5686

    Article  CAS  PubMed  Google Scholar 

  26. Woo S-B, Hellstein JW, Kalmar JR (2006) Systematic review: bisphosphonates and osteonecrosis of the jaws. Ann Internal Med 144:753–761

    Article  CAS  Google Scholar 

  27. Caplan AI (2007) Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J Cell Physiol 213:341–347

    Article  CAS  PubMed  Google Scholar 

  28. Marchionni C, Bonsi L, Alviano F et al (2009) Angiogenic potential of human dental pulp stromal (stem) cells. Int J Immunopathol Pharmacol 22:699–706

    Article  CAS  PubMed  Google Scholar 

  29. Yu J, Wang Y, Deng Z et al (2007) Odontogenic capability: bone marrow stromal stem cells versus dental pulp stem cells. Biol Cell 99:465–474

    Article  PubMed  Google Scholar 

  30. Saoji NA (2008) Effect of bisphosphonate on osteogenic differentiation of pulp and PDL Cells. University of Alabama at Birmingham, Birmingham

    Google Scholar 

  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 44:325–334

    Article  CAS  PubMed  Google Scholar 

  32. Duque G, Rivas D (2007) Alendronate has an anabolic effect on bone through the differentiation of mesenchymal stem cells. J Bone Miner Res 22:1603–1611

    Article  CAS  PubMed  Google Scholar 

  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 26:6941–6949

    Article  CAS  Google Scholar 

  34. Ruggiero SL (2007) Guidelines for the diagnosis of bisphosphonate-related osteonecrosis of the jaw (BRONJ). Clin Cases Min Bone Metabol 4, 37

    Google Scholar 

  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, 167–75

    Article  CAS  PubMed  Google Scholar 

  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 21:905–910

    PubMed  PubMed Central  Google Scholar 

  37. Sharma D, Hamlet SM, Petcu EB, Ivanovski S (2016) The effect of bisphosphonates on the endothelial differentiation of mesenchymal stem cells. Sci Rep 6:20580

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 66:418–427

    Article  CAS  PubMed  Google Scholar 

  39. Berrier AL, Yamada KM (2007) Cell–matrix adhesion. J Cell Physiol 213:565–573

    Article  CAS  PubMed  Google Scholar 

  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 174:194–205

    Article  CAS  PubMed  Google Scholar 

  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 51:1673–1679

    Article  CAS  PubMed  Google Scholar 

  42. Yuasa K, Fukumoto S, Kamasaki Y et al (2004) Laminin α2 is essential for odontoblast differentiation regulating dentin sialoprotein expression. J Biol Chem 279:10286–10292

    Article  CAS  PubMed  Google Scholar 

  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-

    Article  CAS  Google Scholar 

  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:e35685

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 356:780–784

    Article  CAS  PubMed  Google Scholar 

  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 25:1737–1745

    Article  CAS  PubMed  Google Scholar 

  47. Brew K, Nagase H (2010) The tissue inhibitors of metalloproteinases (TIMPs): an ancient family with structural and functional diversity. Biochim Biophys Acta (BBA) 1803:55–71

    Article  CAS  Google Scholar 

  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 109:4055–4063

    Article  CAS  PubMed  Google Scholar 

  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 29:1537–1548

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  1. Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University, Istanbul, Turkey

    Hüseyin Abdik, Ezgi Avşar Abdik, Ayşegül Doğan, Duygu Turan & Fikrettin Şahin

  2. National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, MD, USA

    Selami Demirci

Authors
  1. Hüseyin Abdik
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ezgi Avşar Abdik
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Selami Demirci
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ayşegül Doğan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Duygu Turan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fikrettin Şahin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fikrettin Şahin.

Ethics declarations

Conflict of interest

The authors deny any conflict of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 133756 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Abdik, H., Avşar Abdik, E., Demirci, S. et al. The effects of bisphosphonates on osteonecrosis of jaw bone: a stem cell perspective. Mol Biol Rep 46, 763–776 (2019). https://doi.org/10.1007/s11033-018-4532-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-018-4532-x

Keywords

Search

Navigation