Skip to main content

Advertisement

SpringerLink
Log in

Xenogeneic bone filling materials modulate mesenchymal stem cell recruitment: role of the Complement C5a

  • Original Article
  • Published:
Clinical Oral Investigations Aims and scope Submit manuscript

Abstract

Objectives

When bone filling materials are applied onto the periodontal tissues in vivo, they interact with the injured periodontal ligament (PDL) tissue and modulate its activity. This may lead to mesenchymal stem cells (MSCs) recruitment from bone marrow and initiate bone regeneration. Our hypothesis is that the filling materials affect PDL cells and MSCs functional activities by modulating PDL C5a secretion and subsequent MSCs proliferation and recruitment.

Materials and methods

Materials’ extracts were prepared from 3 bone-grafting materials: Gen-Os® of equine and porcine origins and bovine Bio-Oss®. Expression and secretion of C5a protein by injured PDL cells were investigated by RT-PCR and ELISA. MSCs proliferation was analyzed by MTT assay. C5a binding to MSCs C5aR and its phosphorylation was studied by ELISA. C5a implication in MSCs recruitment toward injured PDL cells was investigated using Boyden chambers.

Results

MSCs proliferation significantly increased with Gen-Os® materials but significantly decreased with Bio-Oss®. C5a secretion slightly increased with Bio-Oss® while its level doubled with Gen-Os® materials. C5a fixation on MSCs C5aR and its phosphorylation significantly increased with Gen-Os® materials but not with Bio-Oss®. MSCs recruitment toward injured PDL cells increased with the three materials but was significantly higher with Gen-Os® materials than with Bio-Oss®. Adding C5a antagonist inhibited MSCs recruitment demonstrating a C5a-mediated migration.

Conclusions

Injured PDL cells secrete C5a leading MSCs proliferation and recruitment to the PDL injured cells. Gen-Os® materials enhanced both C5a secretion by injured PDL cells and MSCs recruitment. Bio-Oss® inhibited MSCs and was less efficient than Gen-Os® materials in inducing MSCs recruitment.

Clinical relevance

Within the limits of this study in vitro, Gen-Os® filling materials have a higher potential than Bio-Oss® on MSCs proliferation and C5a-dependent recruitment to the PDL injury site and the subsequent bone regeneration.

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

Access this article

Log in via an institution

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

Similar content being viewed by others

References

  1. Tan WL, Wong TLT, Wong MCM, Lang NP (2012) A systematic review of post-extractional alveolar hard and soft tissue dimensional changes in humans. Clin Oral Implants Res 23:1–21. https://doi.org/10.1111/j.1600-0501.2011.02375.x

    Article  PubMed  Google Scholar 

  2. Jamjoom A, Cohen RE (2015) Grafts for ridge preservation. J Funct Biomater 6:833–848. https://doi.org/10.3390/jfb6030833

    Article  PubMed  PubMed Central  Google Scholar 

  3. Bassir S, Alhareky M, Wangsrimongkol B, Jia Y, Karimbux N (2018) Systematic review and meta-analysis of hard tissue outcomes of alveolar ridge preservation. Int J Oral Maxillofac Implants 33:979–994. https://doi.org/10.11607/jomi.6399

    Article  PubMed  Google Scholar 

  4. Barone A, Aldini NN, Fini M, Giardino R, Calvo Guirado JL, Covani U (2008) Xenograft versus extraction alone for ridge preservation after tooth removal: a clinical and histomorphometric study. J Periodontol 79:1370–1377. https://doi.org/10.1902/jop.2008.070628

    Article  PubMed  Google Scholar 

  5. Cortellini P (2000) Tonetti MS (2015) Clinical concepts for regenerative therapy in intrabony defects. Periodontol 68:282–307. https://doi.org/10.1111/prd.12048

    Article  Google Scholar 

  6. Giuliani A, Iezzi G, Mazzoni S, Piattelli A, Perrotti V, Barone A (2018) Regenerative properties of collagenated porcine bone grafts in human maxilla: demonstrative study of the kinetics by synchrotron radiation microtomography and light microscopy. Clin Oral Investig 22:505–513. https://doi.org/10.1007/s00784-017-2139-6

    Article  PubMed  Google Scholar 

  7. Alfonsi F, Borgia V, Iezzi G et al (2017) Molecular, cellular and pharmaceutical aspects of filling biomaterials during the management of extraction sockets. Curr Pharm Biotechnol 18:64–75. https://doi.org/10.2174/1389201018666161223152607

    Article  PubMed  Google Scholar 

  8. Lin W, Xu L, Zwingenberger S, Gibon E, Goodman SB, Li G (2017) Mesenchymal stem cells homing to improve bone healing. J Orthop Transl 9:19–27. https://doi.org/10.1016/j.jot.2017.03.002

    Article  Google Scholar 

  9. Wang L, Li Y, Chen J et al (2002) Ischemic cerebral tissue and MCP-1 enhance rat bone marrow stromal cell migration in interface culture. Exp Hematol 30:831–836. https://doi.org/10.1016/S0301-472X(02)00829-9

    Article  PubMed  Google Scholar 

  10. Puré E, Cuff CA (2001) A crucial role for CD44 in inflammation. Trends Mol Med 7:213–221. https://doi.org/10.22203/eCM.v026a09

    Article  PubMed  Google Scholar 

  11. Hemeda H, Jakob M, Ludwig A-K et al (2010) Interferon-gamma and tumor necrosis factor-alpha differentially affect cytokine expression and migration properties of mesenchymal stem cells. Stem Cells Dev 19:693–706. https://doi.org/10.1089/scd.2009.0365

    Article  PubMed  Google Scholar 

  12. Liu J, Kerns DG (2014) Mechanisms of guided bone regeneration: a review. Open Dent J 8:56–65. https://doi.org/10.2174/1874210601408010056

    Article  PubMed  PubMed Central  Google Scholar 

  13. Mijiritsky E, Ferroni L, Gardin C et al (2017) Porcine bone scaffolds adsorb growth factors secreted by MSCs and improve bone tissue repair. Materials 10:1054. https://doi.org/10.3390/ma10091054

    Article  PubMed Central  Google Scholar 

  14. Murphy CM, O’Brien FJ, Little DG, Schindeler A (2013) Cell-scaffold interactions in the bone tissue engineering triad. Eur Cell Mater 26:120–132. https://doi.org/10.22203/eCM.v026a09

    Article  PubMed  Google Scholar 

  15. Ignatius A, Ehrnthaller C, Brenner RE et al (2011) The anaphylatoxin receptor C5aR is present during fracture healing in rats and mediates osteoblast migration in vitro: The Journal of Trauma: Injury. Infect Crit Care 71:952–960. https://doi.org/10.1097/TA.0b013e3181f8aa2d

    Article  Google Scholar 

  16. Ricklin D, Hajishengallis G, Yang K, Lambris JD (2010) Complement: a key system for immune surveillance and homeostasis. Nat Immunol 11:785–797. https://doi.org/10.1038/ni.1923

    Article  PubMed  PubMed Central  Google Scholar 

  17. Giannini E, Boulay F (1995) Phosphorylation, dephosphorylation, and recycling of the C5a receptor in differentiated HL60 cells. J Immunol 154:4055–4064

    PubMed  Google Scholar 

  18. Schraufstatter IU, Discipio RG, Zhao M, Khaldoyanidi SK (2009) C3a and C5a are chemotactic factors for human mesenchymal stem cells, which cause prolonged ERK1/2 phosphorylation. J Immunol 182:3827–3836. https://doi.org/10.4049/jimmunol.0803055

    Article  PubMed  Google Scholar 

  19. Chmilewsky F, Jeanneau C, Laurent P, Kirschfink M, About I (2013) Pulp progenitor cell recruitment is selectively guided by a C5a gradient. J Dent Res 92:532–539. https://doi.org/10.1177/0022034513487377

    Article  PubMed  Google Scholar 

  20. Chmilewsky F, Jeanneau C, Laurent P, About I (2014) Pulp fibroblasts synthesize functional complement proteins involved in initiating dentin-pulp regeneration. Am J Pathol 184:1991–2000. https://doi.org/10.1016/j.ajpath.2014.04.003

    Article  PubMed  Google Scholar 

  21. Li K, Sacks SH, Zhou W (2007) The relative importance of local and systemic complement production in ischaemia, transplantation and other pathologies. Mol Immunol 44:3866–3874. https://doi.org/10.1016/j.molimm.2007.06.006

    Article  PubMed  Google Scholar 

  22. Jeanneau C, Rufas P, Rombouts C et al (2015) Can pulp fibroblasts kill cariogenic bacteria? Role of complement activation. J Dent Res 94:1765–1772. https://doi.org/10.1177/0022034515611074

    Article  PubMed  Google Scholar 

  23. Rombouts C, Jeanneau C, Camilleri J, Laurent P, About I (2016) Characterization and angiogenic potential of xenogeneic bone grafting materials: role of periodontal ligament cells. Dent Mater J 35:900–907. https://doi.org/10.4012/dmj.2016-005

    Article  PubMed  Google Scholar 

  24. Mathieu S, Jeanneau C, Sheibat-Othman N et al (2013) Usefulness of controlled release of growth factors in investigating the early events of dentin-pulp regeneration. J Endod 39:228–235. https://doi.org/10.1016/j.joen.2012.11.007

    Article  PubMed  Google Scholar 

  25. Jia M, Shi Z, Yan X et al (2018) Insulin and heparin-binding epidermal growth factor-like growth factor synergistically promote astrocyte survival and proliferation in serum-free medium. J Neurosci Methods. https://doi.org/10.1016/j.jneumeth.2018.06.002

  26. Morris KM, Aden DP, Knowles BB, Colten HR (1982) Complement biosynthesis by the human hepatoma-derived cell line HepG2. J Clin Invest 70:906–913. https://doi.org/10.1172/JCI110687

    Article  PubMed  PubMed Central  Google Scholar 

  27. Lubbers R, van Essen MF, van Kooten C, Trouw LA (2017) Production of complement components by cells of the immune system: production of complement components. Clin Exp Immunol 188:183–194. https://doi.org/10.1111/cei.12952

    Article  PubMed  PubMed Central  Google Scholar 

  28. Peng Q, Li K, Sacks SH, Zhou W (2009) The role of anaphylatoxins C3a and C5a in regulating innate and adaptive immune responses. Inflamm Allergy Drug Targets 8:236–246. https://doi.org/10.2174/187152809788681038

    Article  PubMed  Google Scholar 

  29. Giraud T, Rufas P, Chmilewsky F et al (2017) Complement activation by pulp capping materials plays a significant role in both inflammatory and pulp stem cells’ recruitment. J Endod 43:1104–1110. https://doi.org/10.1016/j.joen.2017.02.016

    Article  PubMed  Google Scholar 

  30. Zimmermann CE, Gierloff M, Hedderich J, Açil Y, Wiltfang J, Terheyden H (2011) Biocompatibility of bone graft substitutes: effects on survival and proliferation of porcine multilineage stem cells in vitro. Folia Morphol (Warsz) 70:154–160

    Google Scholar 

  31. Adams BR, Mostafa A, Schwartz Z, Boyan BD (2014) Osteoblast response to nanocrystalline calcium hydroxyapatite depends on carbonate content: osteoblasts and Carbonated Hydroxyapatite. J Biomed Mater Res 102:3237–3242. https://doi.org/10.1002/jbm.a.34994

    Article  Google Scholar 

  32. Figueiredo M, Henriques J, Martins G et al (2010) Physicochemical characterization of biomaterials commonly used in dentistry as bone substitutes-comparison with human bone: biomaterials in dentistry as bone substitutes. J Biomed Mater Res 92B:409–419. https://doi.org/10.1002/jbm.b.31529

    Article  Google Scholar 

  33. Barone A, Nannmark U (2014) Bone, biomaterials & beyond. Edra Masson. p 200

  34. Andersson J, Ekdahl KN, Larsson R et al (2002) C3 Adsorbed to a polymer surface can form an initiating alternative pathway convertase. J Immunol 168:5786–5791. https://doi.org/10.4049/jimmunol.168.11.5786

    Article  PubMed  Google Scholar 

  35. Nilsson B, Korsgren O, Lambris JD, Ekdahl KN (2010) Can cells and biomaterials in therapeutic medicine be shielded from innate immune recognition? Trends Immunol 31:32–38. https://doi.org/10.1016/j.it.2009.09.005

    Article  PubMed  PubMed Central  Google Scholar 

  36. Ignatius A, Schoengraf P, Kreja L, Liedert A, Recknagel S, Kandert S, Brenner RE, Schneider M, Lambris JD, Huber-Lang M (2011) Complement C3a and C5a modulate osteoclast formation and inflammatory response of osteoblasts in synergism with IL-1β. J Cell Biochem 112:2594–2605. https://doi.org/10.1002/jcb.23186

    Article  PubMed  PubMed Central  Google Scholar 

  37. Schraufstatter IU (2015) Complement activation in the context of stem cells and tissue repair. World J Stem Cells 7:1090. https://doi.org/10.4252/wjsc.v7.i8.1090

    Article  PubMed  PubMed Central  Google Scholar 

  38. Hutmacher DW (2000) Scaffolds in tissue engineering bone and cartilage. Biomaterials 21:2529–2543. https://doi.org/10.1016/S0142-9612(00)00121-6

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Dr. Jean-Charles GARDON for providing the teeth.

Funding

The work was supported by Aix-Marseille University and CNRS.

Author information

Authors and Affiliations

  1. Aix Marseille Univ, CNRS, ISM, Inst Movement Sci, Marseille, France

    Charlotte Jeanneau, Chloé Le Fournis & Imad About

Authors
  1. Charlotte Jeanneau
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chloé Le Fournis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Imad About
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Imad About.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

For this type of study, formal consent is not required.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jeanneau, C., Le Fournis, C. & About, I. Xenogeneic bone filling materials modulate mesenchymal stem cell recruitment: role of the Complement C5a. Clin Oral Invest 24, 2321–2329 (2020). https://doi.org/10.1007/s00784-019-03087-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00784-019-03087-5

Keywords

Search

Navigation