Table of Contents Author Guidelines Submit a Manuscript
Stem Cells International
Volume 2016 (2016), Article ID 8768162, 16 pages
http://dx.doi.org/10.1155/2016/8768162
Review Article

Medication-Related Osteonecrosis of the Jaw: New Insights into Molecular Mechanisms and Cellular Therapeutic Approaches

1Laboratory of Nervous System Diseases and Therapy, GIGA-Neuroscience, University of Liège, Liège, Belgium
2Department of Maxillofacial Surgery, CHU, University of Liège, Liège, Belgium
3Department of Neurology, CHU, University of Liège, Liège, Belgium

Received 7 July 2016; Accepted 9 August 2016

Academic Editor: Marco Tatullo

Copyright © 2016 Thomas Lombard et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. S. L. Ruggiero, T. B. Dodson, J. Fantasia et al., “American association of oral and maxillofacial surgeons position paper on medication-related osteonecrosis of the jaw—2014 update,” Journal of Oral and Maxillofacial Surgery, vol. 72, no. 10, pp. 1938–1956, 2014. View at Publisher · View at Google Scholar · View at Scopus
  2. T. L. Aghaloo, A. L. Felsenfeld, and S. Tetradis, “Osteonecrosis of the jaw in a patient on denosumab,” Journal of Oral and Maxillofacial Surgery, vol. 68, no. 5, pp. 959–963, 2010. View at Publisher · View at Google Scholar · View at Scopus
  3. K. H. Taylor, L. S. Middlefell, and K. D. Mizen, “Osteonecrosis of the jaws induced by anti-RANK ligand therapy,” British Journal of Oral and Maxillofacial Surgery, vol. 48, no. 3, pp. 221–223, 2010. View at Publisher · View at Google Scholar · View at Scopus
  4. P. Diz, J. L. López-Cedrún, J. Arenaz, and C. Scully, “Denosumab-related osteonecrosis of the jaw,” Journal of the American Dental Association, vol. 143, no. 9, pp. 981–984, 2012. View at Publisher · View at Google Scholar · View at Scopus
  5. A. A. Khan, L. P. Rios, G. K. B. Sándor et al., “Bisphosphonate-associated osteonecrosis of the jaw in Ontario: a survey of oral and maxillofacial surgeons,” Journal of Rheumatology, vol. 38, no. 7, pp. 1396–1402, 2011. View at Publisher · View at Google Scholar · View at Scopus
  6. M. Ulmner, F. Jarnbring, and O. Törring, “Osteonecrosis of the jaw in sweden associated with the oral use of bisphosphonate,” Journal of Oral and Maxillofacial Surgery, vol. 72, no. 1, pp. 76–82, 2014. View at Publisher · View at Google Scholar · View at Scopus
  7. A. A. Khan, A. Morrison, D. A. Hanley et al., “Diagnosis and management of osteonecrosis of the jaw: a systematic review and international consensus,” Journal of Bone and Mineral Research, vol. 30, no. 1, pp. 3–23, 2015. View at Publisher · View at Google Scholar · View at Scopus
  8. A. Barasch, J. Cunha-Cruz, F. A. Curro et al., “Risk factors for osteonecrosis of the jaws: a case-control study from the CONDOR dental PBRN,” Journal of Dental Research, vol. 90, no. 4, pp. 439–444, 2011. View at Publisher · View at Google Scholar
  9. A. O. Hoff, B. B. Toth, K. Altundag et al., “Frequency and risk factors associated with osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates,” Journal of Bone and Mineral Research, vol. 23, no. 6, pp. 826–836, 2008. View at Publisher · View at Google Scholar · View at Scopus
  10. R. Fliefel, M. Tröltzsch, J. Kühnisch, M. Ehrenfeld, and S. Otto, “Treatment strategies and outcomes of bisphosphonate-related osteonecrosis of the jaw (BRONJ) with characterization of patients: a systematic review,” International Journal of Oral and Maxillofacial Surgery, vol. 44, no. 5, pp. 568–585, 2015. View at Publisher · View at Google Scholar · View at Scopus
  11. L. Lum and P. A. Beachy, “The Hedgehog response network: sensors, switches, and routers,” Science, vol. 304, no. 5678, pp. 1755–1759, 2004. View at Publisher · View at Google Scholar · View at Scopus
  12. F. Long, U.-I. Chung, S. Ohba, J. McMahon, H. M. Kronenberg, and A. P. McMahon, “Ihh signaling is directly required for the osteoblast lineage in the endochondral skeleton,” Development, vol. 131, no. 6, pp. 1309–1318, 2004. View at Publisher · View at Google Scholar · View at Scopus
  13. D. Chen, M. Zhao, and G. R. Mundy, “Bone morphogenetic proteins,” Growth Factors, vol. 22, no. 4, pp. 233–241, 2004. View at Publisher · View at Google Scholar · View at Scopus
  14. F. Deschaseaux, L. Sensébé, and D. Heymann, “Mechanisms of bone repair and regeneration,” Trends in Molecular Medicine, vol. 15, no. 9, pp. 417–429, 2009. View at Publisher · View at Google Scholar · View at Scopus
  15. N. Holleville, S. Matéos, M. Bontoux, K. Bollerot, and A.-H. Monsoro-Burq, “Dlx5 drives Runx2 expression and osteogenic differentiation in developing cranial suture mesenchyme,” Developmental Biology, vol. 304, no. 2, pp. 860–874, 2007. View at Publisher · View at Google Scholar · View at Scopus
  16. F. Liu, S. Kohlmeier, and C.-Y. Wang, “Wnt signaling and skeletal development,” Cellular Signalling, vol. 20, no. 6, pp. 999–1009, 2008. View at Publisher · View at Google Scholar · View at Scopus
  17. J. C. Frith, J. Mönkkönen, S. Auriola, H. Mönkkönen, and M. J. Rogers, “The molecular mechanism of action of the antiresorptive and antiinflammatory drug clodronate: evidence for the formation in vivo of a metabolite that inhibits bone resorption and causes osteoclast and macrophage apoptosis,” Arthritis and Rheumatism, vol. 44, no. 9, pp. 2201–2210, 2001. View at Publisher · View at Google Scholar · View at Scopus
  18. J. E. Dunford, K. Thompson, F. P. Coxon et al., “Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates,” Journal of Pharmacology and Experimental Therapeutics, vol. 296, no. 2, pp. 235–242, 2001. View at Google Scholar · View at Scopus
  19. K. Thompson, A. J. Roelofs, M. Jauhiainen, H. Mönkkönen, J. Mönkkönen, and M. J. Rogers, “Activation of γδ T cells by bisphosphonates,” in Osteoimmunology, vol. 658 of Advances in Experimental Medicine and Biology, pp. 11–20, Springer, Boston, Mass, USA, 2010. View at Publisher · View at Google Scholar
  20. I. S. Hamadeh, B. A. Ngwa, and Y. Gong, “Drug induced osteonecrosis of the jaw,” Cancer Treatment Reviews, vol. 41, no. 5, pp. 455–464, 2015. View at Publisher · View at Google Scholar · View at Scopus
  21. V. Ribeiro, M. Garcia, R. Oliveira, P. S. Gomes, B. Colaço, and M. H. Fernandes, “Bisphosphonates induce the osteogenic gene expression in co-cultured human endothelial and mesenchymal stem cells,” Journal of Cellular and Molecular Medicine, vol. 18, no. 1, pp. 27–37, 2014. View at Publisher · View at Google Scholar · View at Scopus
  22. D. L. Kendler, C. Roux, C. L. Benhamou et al., “Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy,” Journal of Bone and Mineral Research, vol. 25, no. 1, pp. 72–81, 2010. View at Publisher · View at Google Scholar · View at Scopus
  23. D. A. Hanley, J. D. Adachi, A. Bell, and V. Brown, “Denosumab: mechanism of action and clinical outcomes,” International Journal of Clinical Practice, vol. 66, no. 12, pp. 1139–1146, 2012. View at Publisher · View at Google Scholar · View at Scopus
  24. F. Giancola, G. Campisi, L. Lo Russo, L. L. Muzio, and O. Di Fede, “Osteonecrosis of the jaw related to everolimus and bisphosphonate: a unique case report?” Annali di Stomatologia, vol. 4, supplement 2, pp. 20–21, 2013. View at Google Scholar
  25. D. W. Kim, Y.-S. Jung, H.-S. Park, and H.-D. Jung, “Osteonecrosis of the jaw related to everolimus: a case report,” British Journal of Oral and Maxillofacial Surgery, vol. 51, no. 8, pp. e302–e304, 2013. View at Publisher · View at Google Scholar · View at Scopus
  26. S. Hoefert, I. Schmitz, A. Tannapfel, and H. Eufinger, “Importance of microcracks in etiology of bisphosphonate-related osteonecrosis of the jaw: a possible pathogenetic model of symptomatic and non-symptomatic osteonecrosis of the jaw based on scanning electron microscopy findings,” Clinical Oral Investigations, vol. 14, no. 3, pp. 271–284, 2010. View at Publisher · View at Google Scholar · View at Scopus
  27. B. Kang, S. Cheong, T. Chaichanasakul et al., “Periapical disease and bisphosphonates induce osteonecrosis of the jaws in mice,” Journal of Bone and Mineral Research, vol. 28, no. 7, pp. 1631–1640, 2013. View at Publisher · View at Google Scholar · View at Scopus
  28. T. L. Aghaloo, B. Kang, E. C. Sung et al., “Periodontal disease and bisphosphonates induce osteonecrosis of the jaws in the rat,” Journal of Bone and Mineral Research, vol. 26, no. 8, pp. 1871–1882, 2011. View at Publisher · View at Google Scholar · View at Scopus
  29. P. Lesclous, S. Abi Najm, J.-P. Carrel et al., “Bisphosphonate-associated osteonecrosis of the jaw: a key role of inflammation?” Bone, vol. 45, no. 5, pp. 843–852, 2009. View at Publisher · View at Google Scholar · View at Scopus
  30. A. Cheung and E. Seeman, “Teriparatide therapy for alendronate-associated osteonecrosis of the jaw,” The New England Journal of Medicine, vol. 363, no. 25, pp. 2473–2474, 2010. View at Publisher · View at Google Scholar · View at Scopus
  31. A. Bramati, S. Girelli, G. Farina et al., “Prospective, mono-institutional study of the impact of a systematic prevention program on incidence and outcome of osteonecrosis of the jaw in patients treated with bisphosphonates for bone metastases,” Journal of Bone and Mineral Metabolism, vol. 33, no. 1, pp. 119–124, 2015. View at Publisher · View at Google Scholar · View at Scopus
  32. R. E. Marx, Y. Sawatari, M. Fortin, and V. Broumand, “Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment,” Journal of Oral and Maxillofacial Surgery, vol. 63, no. 11, pp. 1567–1575, 2005. View at Publisher · View at Google Scholar · View at Scopus
  33. P. P. Sedghizadeh, S. K. S. Kumar, A. Gorur, C. Schaudinn, C. F. Shuler, and J. W. Costerton, “Identification of microbial biofilms in osteonecrosis of the jaws secondary to bisphosphonate therapy,” Journal of Oral and Maxillofacial Surgery, vol. 66, no. 4, pp. 767–775, 2008. View at Publisher · View at Google Scholar · View at Scopus
  34. S. L. Ruggiero, E. R. Carlson, and L. A. Assael, “Comprehensive review of bisphosphonate therapy: implications for the oral and maxillofacial surgery patient,” Journal of Oral and Maxillofacial Surgery, vol. 67, no. 5, supplement, p. 1, 2009. View at Publisher · View at Google Scholar · View at Scopus
  35. Y. Chai and R. E. Maxson Jr., “Recent advances in craniofacial morphogenesis,” Developmental Dynamics, vol. 235, no. 9, pp. 2353–2375, 2006. View at Publisher · View at Google Scholar · View at Scopus
  36. P. Leucht, J.-B. Kim, R. Amasha, A. W. James, S. Girod, and J. A. Helms, “Embryonic origin and Hox status determine progenitor cell fate during adult bone regeneration,” Development, vol. 135, no. 17, pp. 2845–2854, 2008. View at Publisher · View at Google Scholar · View at Scopus
  37. H. Akiyama, M.-C. Chaboissier, J. F. Martin, A. Schedl, and B. De Crombrugghe, “The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6,” Genes and Development, vol. 16, no. 21, pp. 2813–2828, 2002. View at Publisher · View at Google Scholar · View at Scopus
  38. E. Hinoi, P. Bialek, Y.-T. Chen et al., “Runx2 inhibits chondrocyte proliferation and hypertrophy through its expression in the perichondrium,” Genes and Development, vol. 20, no. 21, pp. 2937–2942, 2006. View at Publisher · View at Google Scholar · View at Scopus
  39. R. F. Robledo, L. Rajan, X. Li, and T. Lufkin, “The D1x5 and D1x6 homeobox genes are essential for craniofacial, axial, and appendicular skeletal development,” Genes and Development, vol. 16, no. 9, pp. 1089–1101, 2002. View at Publisher · View at Google Scholar · View at Scopus
  40. W.-Y. Baek, M.-A. Lee, W. J. Ji et al., “Positive regulation of adult bone formation by osteoblast-specific transcription factor osterix,” Journal of Bone and Mineral Research, vol. 24, no. 6, pp. 1055–1065, 2009. View at Publisher · View at Google Scholar · View at Scopus
  41. R. P. Harper and E. Fung, “Resolution of bisphosphonate-associated osteonecrosis of the mandible: possible application for intermittent low-dose parathyroid hormone [rhPTH(1-34)],” Journal of Oral and Maxillofacial Surgery, vol. 65, no. 3, pp. 573–580, 2007. View at Publisher · View at Google Scholar · View at Scopus
  42. M. Cicciù, A. S. Herford, G. Juodžbalys, and E. Stoffella, “Recombinant human bone morphogenetic protein type 2 application for a possible treatment of bisphosphonates-related osteonecrosis of the jaw,” Journal of Craniofacial Surgery, vol. 23, no. 3, pp. 784–788, 2012. View at Publisher · View at Google Scholar · View at Scopus
  43. F. Morvan, K. Boulukos, P. Clément-Lacroix et al., “Deletion of a single allele of the Dkk1 gene leads to an increase in bone formation and bone mass,” Journal of Bone and Mineral Research, vol. 21, no. 6, pp. 934–945, 2006. View at Publisher · View at Google Scholar · View at Scopus
  44. D. J. Heath, A. D. Chantry, C. H. Buckle et al., “Inhibiting Dickkopf-1 (Dkk1) removes suppression of bone formation and prevents the development of osteolytic bone disease in multiple myeloma,” Journal of Bone and Mineral Research, vol. 24, no. 3, pp. 425–436, 2009. View at Publisher · View at Google Scholar · View at Scopus
  45. S. J. Rodda and A. P. McMahon, “Distinct roles for Hedgehog and caronical Wnt signaling in specification, differentiation and maintenance of osteoblast progenitors,” Development, vol. 133, no. 16, pp. 3231–3244, 2006. View at Publisher · View at Google Scholar · View at Scopus
  46. X. Li, M. S. Ominsky, K. S. Warmington et al., “Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis,” Journal of Bone and Mineral Research, vol. 24, no. 4, pp. 578–588, 2009. View at Publisher · View at Google Scholar · View at Scopus
  47. M. Asagiri, K. Sato, T. Usami et al., “Autoamplification of NFATc1 expression determines its essential role in bone homeostasis,” The Journal of Experimental Medicine, vol. 202, no. 9, pp. 1261–1269, 2005. View at Publisher · View at Google Scholar · View at Scopus
  48. T. J. Yun, P. M. Chaudhary, G. L. Shu et al., “OPG/FDCR-1, a TNF receptor family member, is expressed in lymphoid cells and is up-regulated by ligating CD40,” The Journal of Immunology, vol. 161, no. 11, pp. 6113–6121, 1998. View at Google Scholar · View at Scopus
  49. M. M. Guerrini and H. Takayanagi, “The immune system, bone and RANKL,” Archives of Biochemistry and Biophysics, vol. 561, pp. 118–123, 2014. View at Publisher · View at Google Scholar · View at Scopus
  50. T. Nakashima and H. Takayanagi, “Osteoimmunology: crosstalk between the immune and bone systems,” Journal of Clinical Immunology, vol. 29, no. 5, pp. 555–567, 2009. View at Publisher · View at Google Scholar · View at Scopus
  51. L. C. de Rezende, I. V. Silva, L. B. Rangel, and M. C. Guimarães, “Regulatory T cell as a target for cancer therapy,” Archivum Immunologiae et Therapiae Experimentalis, vol. 58, no. 3, pp. 179–190, 2010. View at Publisher · View at Google Scholar
  52. K. Nakamura, A. Kitani, and W. Strober, “Cell contact–dependent immunosuppression by CD4+CD25+regulatory T cells is mediated by cell surface–bound transforming growth factor β,” Journal of Experimental Medicine, vol. 194, no. 5, pp. 629–644, 2001. View at Publisher · View at Google Scholar · View at Scopus
  53. J. D. Fontenot, M. A. Gavin, and A. Y. Rudensky, “Foxp3 programs the development and function of CD4+CD25+ regulatory T cells,” Nature Immunology, vol. 4, no. 4, pp. 330–336, 2003. View at Publisher · View at Google Scholar · View at Scopus
  54. M. M. Zaiss, R. Axmann, J. Zwerina et al., “Treg cells suppress osteoclast formation: a new link between the immune system and bone,” Arthritis and Rheumatism, vol. 56, no. 12, pp. 4104–4112, 2007. View at Publisher · View at Google Scholar · View at Scopus
  55. Y. G. Kim, C.-K. Lee, S.-S. Nah, S. H. Mun, B. Yoo, and H.-B. Moon, “Human CD4+CD25+ regulatory T cells inhibit the differentiation of osteoclasts from peripheral blood mononuclear cells,” Biochemical and Biophysical Research Communications, vol. 357, no. 4, pp. 1046–1052, 2007. View at Publisher · View at Google Scholar · View at Scopus
  56. A. C. Hayday, “γδ Cells: a right time and a right place for a conserved third way of protection,” Annual Review of Immunology, vol. 18, pp. 975–1026, 2000. View at Publisher · View at Google Scholar · View at Scopus
  57. A. Pappalardo and K. Thompson, “Activated γδ T cells inhibit osteoclast differentiation and resorptive activity in vitro,” Clinical & Experimental Immunology, vol. 174, no. 2, pp. 281–291, 2013. View at Publisher · View at Google Scholar · View at Scopus
  58. N. Komatsu, K. Okamoto, S. Sawa et al., “Pathogenic conversion of Foxp3+ T cells into TH17 cells in autoimmune arthritis,” Nature Medicine, vol. 20, no. 1, pp. 62–68, 2014. View at Publisher · View at Google Scholar · View at Scopus
  59. A. Picchianti Diamanti, M. M. Rosado, M. Scarsella et al., “Abatacept (cytotoxic T lymphocyte antigen 4-immunoglobulin) improves B cell function and regulatory T cell inhibitory capacity in rheumatoid arthritis patients non-responding to anti-tumour necrosis factor-α agents,” Clinical and Experimental Immunology, vol. 177, no. 3, pp. 630–640, 2014. View at Publisher · View at Google Scholar · View at Scopus
  60. A. Bozec, M. M. Zaiss, R. Kagwiria et al., “T cell costimulation molecules CD80/86 inhibit osteoclast differentiation by inducing the IDO/tryptophan pathway,” Science Translational Medicine, vol. 6, Article ID 235ra60, 2014. View at Publisher · View at Google Scholar · View at Scopus
  61. T. Yoshitaka, T. Mukai, M. Kittaka et al., “Enhanced TLR-MYD88 signaling stimulates autoinflammation in SH3BP2 cherubism mice and defines the etiology of cherubism,” Cell Reports, vol. 8, no. 6, pp. 1752–1766, 2014. View at Publisher · View at Google Scholar · View at Scopus
  62. P. Saftig, E. Hunziker, O. Wehmeyer et al., “Impaired osteoclastic bone resorption leads to osteopetrosis in cathepsin-K-deficient mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 23, pp. 13453–13458, 1998. View at Publisher · View at Google Scholar · View at Scopus
  63. M. Asagiri, T. Hirai, T. Kunigami et al., “Cathepsin K-dependent toll-like receptor 9 signaling revealed in experimental arthritis,” Science, vol. 319, no. 5863, pp. 624–627, 2008. View at Publisher · View at Google Scholar · View at Scopus
  64. N. Suzuki, K. Takimoto, and N. Kawashima, “Cathepsin K inhibitor regulates inflammation and bone destruction in experimentally induced rat periapical lesions,” Journal of Endodontics, vol. 41, no. 9, pp. 1474–1479, 2015. View at Publisher · View at Google Scholar · View at Scopus
  65. R. D. Chapurlat, “Odanacatib: a review of its potential in the management of osteoporosis in postmenopausal women,” Therapeutic Advances in Musculoskeletal Disease, vol. 7, no. 3, pp. 103–109, 2015. View at Publisher · View at Google Scholar · View at Scopus
  66. P. Lesclous, S. Grabar, S. Abi Najm et al., “Relevance of surgical management of patients affected by bisphosphonate-associated osteonecrosis of the jaws. A Prospective Clinical and Radiological Study,” Clinical Oral Investigations, vol. 18, no. 2, pp. 391–399, 2014. View at Publisher · View at Google Scholar · View at Scopus
  67. E. Quattrocchi and H. Kourlas, “Teriparatide: a review,” Clinical Therapeutics, vol. 26, no. 6, pp. 841–854, 2004. View at Publisher · View at Google Scholar · View at Scopus
  68. P. C. Bessa, M. Casal, and R. L. Reis, “Bone morphogenetic proteins in tissue engineering: the road from the laboratory to the clinic, part I (basic concepts),” Journal of Tissue Engineering and Regenerative Medicine, vol. 2, no. 1, pp. 1–13, 2008. View at Publisher · View at Google Scholar · View at Scopus
  69. A. C. Carreira, F. H. Lojudice, E. Halcsik, R. D. Navarro, M. C. Sogayar, and J. M. Granjeiro, “Bone morphogenetic proteins: facts, challenges, and future perspectives,” Journal of Dental Research, vol. 93, no. 4, pp. 335–345, 2014. View at Publisher · View at Google Scholar · View at Scopus
  70. N. S. Arora, T. Ramanayake, Y.-F. Ren, and G. E. Romanos, “Platelet-rich plasma: a literature review,” Implant Dentistry, vol. 18, no. 4, pp. 303–310, 2009. View at Publisher · View at Google Scholar · View at Scopus
  71. D. M. Dohan Ehrenfest, L. Rasmusson, and T. Albrektsson, “Classification of platelet concentrates: from pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (L-PRF),” Trends in Biotechnology, vol. 27, no. 3, pp. 158–167, 2009. View at Publisher · View at Google Scholar · View at Scopus
  72. F. Longo, A. Guida, C. Aversa et al., “Platelet rich plasma in the treatment of bisphosphonate-related osteonecrosis of the jaw: personal experience and review of the literature,” International Journal of Dentistry, vol. 2014, Article ID 298945, 7 pages, 2014. View at Publisher · View at Google Scholar · View at Scopus
  73. J.-W. Kim, S.-J. Kim, and M.-R. Kim, “Leucocyte-rich and platelet-rich fibrin for the treatment of bisphosphonate-related osteonecrosis of the jaw: A Prospective Feasibility Study,” British Journal of Oral and Maxillofacial Surgery, vol. 52, no. 9, pp. 854–859, 2014. View at Publisher · View at Google Scholar · View at Scopus
  74. P. A. M. Everts, A. van Zundert, J. P. A. M. Schönberger, R. J. J. Devilee, and J. T. A. Knape, “What do we use: platelet-rich plasma or platelet-leukocyte gel?” Journal of Biomedical Materials Research A, vol. 85, no. 4, pp. 1135–1136, 2008. View at Publisher · View at Google Scholar · View at Scopus
  75. D. M. Dohan, J. Choukroun, A. Diss et al., “Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part III: leucocyte activation: a new feature for platelet concentrates?” Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontology, vol. 101, no. 3, pp. e51–e55, 2006. View at Publisher · View at Google Scholar · View at Scopus
  76. M. Del Fabbro, G. Gallesio, and M. Mozzati, “Autologous platelet concentrates for bisphosphonate-related osteonecrosis of the jaw treatment and prevention. A systematic review of the literature,” European Journal of Cancer, vol. 51, no. 1, pp. 62–74, 2015. View at Publisher · View at Google Scholar · View at Scopus
  77. R. Gianni-Barrera, M. Bartolomeo, B. Vollmar, V. Djonov, and A. Banfi, “Split for the cure: VEGF, PDGF-BB and intussusception in therapeutic angiogenesis,” Biochemical Society Transactions, vol. 42, no. 6, pp. 1637–1642, 2014. View at Publisher · View at Google Scholar · View at Scopus
  78. H. Xie, Z. Cui, L. Wang et al., “PDGF-BB secreted by preosteoclasts induces angiogenesis during coupling with osteogenesis,” Nature Medicine, vol. 20, no. 11, pp. 1270–1278, 2014. View at Publisher · View at Google Scholar · View at Scopus
  79. P. Vescovi, I. Giovannacci, S. Otto et al., “Medication-related osteonecrosis of the jaw: an autofluorescence-guided surgical approach performed with Er:YAG laser,” Photomedicine and Laser Surgery, vol. 33, no. 8, pp. 437–442, 2015. View at Publisher · View at Google Scholar · View at Scopus
  80. P. Vescovi, M. Meleti, E. Merigo et al., “Case series of 589 tooth extractions in patients under bisphosphonates therapy. Proposal of a clinical protocol supported by Nd: YAG low-level laser therapy,” Medicina Oral, Patologia Oral y Cirugia Bucal, vol. 18, no. 4, pp. e680–e685, 2013. View at Publisher · View at Google Scholar · View at Scopus
  81. M. A. Altay, F. Tasar, E. Tosun, and B. Kan, “Low-level laser therapy supported surgical treatment of bisphosphonate related osteonecrosis of jaws: a retrospective analysis of 11 cases,” Photomedicine and Laser Surgery, vol. 32, no. 8, pp. 468–475, 2014. View at Publisher · View at Google Scholar · View at Scopus
  82. G. A. Guzzardella, M. Fini, P. Torricelli, G. Giavaresi, and R. Giardino, “Laser stimulation on bone defect healing: an in vitro study,” Lasers in Medical Science, vol. 17, no. 3, pp. 216–220, 2002. View at Publisher · View at Google Scholar · View at Scopus
  83. Y. Ueda and N. Shimizu, “Effects of Pulse Frequency of Low-Level Laser Therapy (LLLT) on Bone nodule formation in rat calvarial cells,” Journal of Clinical Laser Medicine and Surgery, vol. 21, no. 5, pp. 271–277, 2003. View at Publisher · View at Google Scholar · View at Scopus
  84. R. E. Marx, “A new concept in the treatment of osteoradionecrosis,” Journal of Oral and Maxillofacial Surgery, vol. 41, no. 6, pp. 351–357, 1983. View at Publisher · View at Google Scholar · View at Scopus
  85. D. R. Knighton, V. D. Fiegel, T. Halverson, S. Schneider, T. Brown, and C. L. Wells, “Oxygen as an antibiotic. The effect of inspired oxygen on bacterial clearance,” Archives of Surgery, vol. 125, no. 1, pp. 97–100, 1990. View at Publisher · View at Google Scholar · View at Scopus
  86. J. J. Freiberger, “Utility of hyperbaric oxygen in treatment of bisphosphonate-related osteonecrosis of the jaws,” Journal of Oral and Maxillofacial Surgery, vol. 67, no. 5, pp. 96–106, 2009. View at Publisher · View at Google Scholar · View at Scopus
  87. J. V. Boykin Jr. and C. Baylis, “Hyperbaric oxygen therapy mediates increased nitric oxide production associated with wound healing: a preliminary study,” Advances in Skin & Wound Care, vol. 20, no. 7, pp. 382–388, 2007. View at Publisher · View at Google Scholar · View at Scopus
  88. J. J. Freiberger, R. Padilla-Burgos, A. H. Chhoeu et al., “Hyperbaric oxygen treatment and bisphosphonate-induced osteonecrosis of the jaw: a case series,” Journal of Oral and Maxillofacial Surgery, vol. 65, no. 7, pp. 1321–1327, 2007. View at Publisher · View at Google Scholar · View at Scopus
  89. J. J. Freiberger, R. Padilla-Burgos, T. McGraw et al., “What is the role of hyperbaric oxygen in the management of bisphosphonate-related osteonecrosis of the jaw: a randomized controlled trial of hyperbaric oxygen as an adjunct to surgery and antibiotics,” Journal of Oral and Maxillofacial Surgery, vol. 70, no. 7, pp. 1573–1583, 2012. View at Publisher · View at Google Scholar · View at Scopus
  90. A. Dyas, B. J. Boughton, and B. C. Das, “Ozone killing action against bacterial and fungal species; microbiological testing of a domestic ozone generator,” Journal of Clinical Pathology, vol. 36, no. 10, pp. 1102–1104, 1983. View at Publisher · View at Google Scholar · View at Scopus
  91. V. Bocci, “Ozone as Janus: this controversial gas can be either toxic or medically useful,” Mediators of Inflammation, vol. 13, no. 1, pp. 3–11, 2004. View at Publisher · View at Google Scholar · View at Scopus
  92. A. Agrillo, F. Filiaci, V. Ramieri et al., “Bisphosphonate-related osteonecrosis of the jaw (BRONJ): 5 year experience in the treatment of 131 cases with ozone therapy,” European Review for Medical and Pharmacological Sciences, vol. 16, no. 12, pp. 1741–1747, 2012. View at Google Scholar · View at Scopus
  93. A. Agrillo, P. Sassano, C. Rinna, P. Priore, and G. Iannetti, “Ozone therapy in extractive surgery on patients treated with bisphosphonates,” Journal of Craniofacial Surgery, vol. 18, no. 5, pp. 1068–1070, 2007. View at Publisher · View at Google Scholar · View at Scopus
  94. M. Dominici, K. Le Blanc, I. Mueller et al., “Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement,” Cytotherapy, vol. 8, no. 4, pp. 315–317, 2006. View at Publisher · View at Google Scholar · View at Scopus
  95. M. Crisan, S. Yap, L. Casteilla et al., “A perivascular origin for mesenchymal stem cells in multiple human organs,” Cell Stem Cell, vol. 3, no. 3, pp. 301–313, 2008. View at Publisher · View at Google Scholar · View at Scopus
  96. M. Di Ianni, B. Del Papa, M. De Ioanni et al., “Mesenchymal cells recruit and regulate T regulatory cells,” Experimental Hematology, vol. 36, no. 3, pp. 309–318, 2008. View at Publisher · View at Google Scholar · View at Scopus
  97. M. J. Robertson and J. Ritz, “Biology and clinical relevance of human natural killer cells,” Blood, vol. 76, no. 12, pp. 2421–2438, 1990. View at Google Scholar · View at Scopus
  98. G. M. Spaggiari, A. Capobianco, H. Abdelrazik, F. Becchetti, M. C. Mingari, and L. Moretta, “Mesenchymal stem cells inhibit natural killer-cell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2,3-dioxygenase and prostaglandin E2,” Blood, vol. 111, no. 3, pp. 1327–1333, 2008. View at Publisher · View at Google Scholar · View at Scopus
  99. M. Rossi and J. W. Young, “Human dendritic cells: potent antigen-presenting cells at the crossroads of innate and adaptive immunity,” Journal of Immunology, vol. 175, no. 3, pp. 1373–1381, 2005. View at Publisher · View at Google Scholar · View at Scopus
  100. G. M. Spaggiari, H. Abdelrazik, F. Becchetti, and L. Moretta, “MSCs inhibit monocyte-derived DC maturation and function by selectively interfering with the generation of immature DCs: central role of MSC-derived prostaglandin E2,” Blood, vol. 113, no. 26, pp. 6576–6583, 2009. View at Publisher · View at Google Scholar · View at Scopus
  101. Y.-P. Li, S. Paczesny, E. Lauret et al., “Human mesenchymal stem cells license adult CD34+ hemopoietic progenitor cells to differentiate into regulatory dendritic cells through activation of the notch pathway,” Journal of Immunology, vol. 180, no. 3, pp. 1598–1608, 2008. View at Publisher · View at Google Scholar · View at Scopus
  102. A. Mantovani, A. Sica, and M. Locati, “Macrophage polarization comes of age,” Immunity, vol. 23, no. 4, pp. 344–346, 2005. View at Publisher · View at Google Scholar · View at Scopus
  103. N. Mokarram and R. V. Bellamkonda, “A perspective on immunomodulation and tissue repair,” Annals of Biomedical Engineering, vol. 42, no. 2, pp. 338–351, 2014. View at Publisher · View at Google Scholar · View at Scopus
  104. H. Nakajima, K. Uchida, A. R. Guerrero et al., “Transplantation of mesenchymal stem cells promotes an alternative pathway of macrophage activation and functional recovery after spinal cord injury,” Journal of Neurotrauma, vol. 29, no. 8, pp. 1614–1625, 2012. View at Publisher · View at Google Scholar · View at Scopus
  105. S. Tabera, J. A. Pérez-Simón, M. Díez-Campelo et al., “The effect of mesenchymal stem cells on the viability, proliferation and differentiation of B-lymphocytes,” Haematologica, vol. 93, no. 9, pp. 1301–1309, 2008. View at Publisher · View at Google Scholar · View at Scopus
  106. M. Krampera, L. Cosmi, R. Angeli et al., “Role for interferon-γ in the immunomodulatory activity of human bone marrow mesenchymal stem cells,” Stem Cells, vol. 24, no. 2, pp. 386–398, 2006. View at Publisher · View at Google Scholar · View at Scopus
  107. C. Prevosto, M. Zancolli, P. Canevali, M. R. Zocchi, and A. Poggi, “Generation of CD4+ or CD8+ regulatory T cells upon mesenchymal stem cell-lymphocyte interaction,” Haematologica, vol. 92, no. 7, pp. 881–888, 2007. View at Publisher · View at Google Scholar · View at Scopus
  108. S. Ghannam, C. Bouffi, F. Djouad, C. Jorgensen, and D. Noël, “Immunosuppression by mesenchymal stem cells: mechanisms and clinical applications,” Stem Cell Research and Therapy, vol. 1, article 2, 2010. View at Publisher · View at Google Scholar · View at Scopus
  109. L. Bai, D. P. Lennon, V. Eaton et al., “Human bone marrow-derived mesenchymal stem cells induce Th2-polarized immune response and promote endogenous repair in animal models of multiple sclerosis,” Glia, vol. 57, no. 11, pp. 1192–1203, 2009. View at Publisher · View at Google Scholar · View at Scopus
  110. K. Sato, K. Ozaki, I. Oh et al., “Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells,” Blood, vol. 109, no. 1, pp. 228–234, 2007. View at Publisher · View at Google Scholar · View at Scopus
  111. R. Meisel, A. Zibert, M. Laryea, U. Göbel, W. Däubener, and D. Dilloo, “Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation,” Blood, vol. 103, no. 12, pp. 4619–4621, 2004. View at Publisher · View at Google Scholar · View at Scopus
  112. Y. Wang, X. Chen, W. Cao, and Y. Shi, “Plasticity of mesenchymal stem cells in immunomodulation: pathological and therapeutic implications,” Nature Immunology, vol. 15, no. 11, pp. 1009–1016, 2014. View at Publisher · View at Google Scholar · View at Scopus
  113. T. Kikuiri, I. Kim, T. Yamaza et al., “Cell-based immunotherapy with mesenchymal stem cells cures bisphosphonate-related osteonecrosis of the jaw-like disease in mice,” Journal of Bone and Mineral Research, vol. 25, no. 7, pp. 1668–1679, 2010. View at Publisher · View at Google Scholar · View at Scopus
  114. Y. Li, J. Xu, L. Mao et al., “Allogeneic mesenchymal stem cell therapy for bisphosphonate-related jaw osteonecrosis in swine,” Stem Cells and Development, vol. 22, no. 14, pp. 2047–2056, 2013. View at Publisher · View at Google Scholar · View at Scopus
  115. L. Cella, A. Oppici, M. Arbasi et al., “Autologous bone marrow stem cell intralesional transplantation repairing bisphosphonate related osteonecrosis of the jaw,” Head and Face Medicine, vol. 7, article 16, 2011. View at Publisher · View at Google Scholar · View at Scopus
  116. C. E. Zimmermann, M. Gierloff, J. Hedderich, Y. Açil, J. Wiltfang, and H. Terheyden, “Survival of transplanted rat bone marrow-derived osteogenic stem cells in vivo,” Tissue Engineering—Part A, vol. 17, no. 7-8, pp. 1147–1156, 2011. View at Publisher · View at Google Scholar · View at Scopus
  117. V. Neirinckx, D. Cantinieaux, C. Coste, B. Rogister, R. Franzen, and S. Wislet-Gendebien, “Concise review: spinal cord injuries: how could adult mesenchymal and neural crest stem cells take up the challenge,” STEM CELLS, vol. 32, no. 4, pp. 829–843, 2014. View at Publisher · View at Google Scholar · View at Scopus
  118. K. Ogata, W. Katagiri, M. Osugi et al., “Evaluation of the therapeutic effects of conditioned media from mesenchymal stem cells in a rat bisphosphonate-related osteonecrosis of the jaw-like model,” Bone, vol. 74, pp. 95–105, 2015. View at Publisher · View at Google Scholar · View at Scopus