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The effect of laser therapy on the expression of osteocalcin and osteopontin after tooth extraction in rats treated with zoledronate and dexamethasone

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Abstract

Purpose

Laser therapy has been used for the prevention and management of medication-related ostenecrosis of the jaw (MRONJ). The aim of this paper was to investigate the action of laser therapy on extraction socket healing in rats in conditions at risk for MRONJ, evaluating the expression of markers of bone metabolism.

Methods

Thirty male Sprague–Dawley rats were divided in four groups: control group (C, n = 5), laser group (L, n = 5), treatment group (T, n = 10), and treatment plus laser group (T + L, n = 10). Rats of group T and T + L received zoledronate 0.1 mg/kg and dexamethasone 1 mg/kg every 2 days for 10 weeks. Rats of group C and L were infused with vehicle. After 9 weeks, the left maxillary molars were extracted in all rats. Rats of groups L and T + L received laser therapy (Nd:YAG, 1064 nm, 1.25 W, 15 Hz, 5 min, 14.37 J/cm2) in the socket area at days 0, 2, 4, and 6 after surgery. Western blot analysis was performed to evaluate the alveolar expression of osteopontin (OPN) and osteocalcin (OCN) 8 days after extraction.

Results

Rats of groups L and T + L showed a significant higher expression of OCN compared to rats of groups C and T (+348 and +400 %, respectively; P = 0.013 and P = 0.002, respectively). The expression of OPN did not show significant differences among the different groups.

Conclusions

Our findings suggest that laser irradiation after tooth extraction can promote osteoblast differentiation, as demonstrated by the higher expression of OCN. Thus, laser irradiation could be considered a way to improve socket healing in conditions at risk for MRONJ development.

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References

  1. Ruggiero SL, Dodson TB, Fantasia J, Goodday R, Aghaloo T, Mehrotra B, O'Ryan F (2014) American Association of Oral and Maxillofacial Surgeons Position Paper on Medication-Related Osteonecrosis of the Jaw-2014 Update. J Oral Maxillofac Surg 72:1938–1956

    Article  PubMed  Google Scholar 

  2. Devlin H, Garland H, Sloan P (1996) Healing of tooth extraction sockets in experimental diabetes mellitus. J Oral Maxillofac Surg 54:1087–1091

    Article  PubMed  CAS  Google Scholar 

  3. Aguirre JI, Altman MK, Vanegas SM, Franz SE, Bassit ACF, Wronski TJ (2010) Effects of alendronate on bone healing after tooth extraction in rats. Oral Dis 16:674–685

    Article  PubMed  CAS  Google Scholar 

  4. Shyng YC, Devlin H, Riccardi D, Sloan P (1999) Expression of cartilage-derived retinoic acid-sensitive protein during healing of the rat tooth-extraction socket. Arch Oral Biol 44:751–757

    Article  PubMed  CAS  Google Scholar 

  5. Barba-Recreo P, Pardo DC, de Vera JL, García-Arranz M, Yébenes L, Burgueño M (2014) Zoledronic acid - related osteonecrosis of the jaws. Experimental model with dental extractions in rats. J Craniomaxillofac Surg 42:744–750

    Article  PubMed  Google Scholar 

  6. Heufelder MJ, Hendricks J, Remmerbach T, Frerich B, Hemprich A, Wilde F (2014) Principles of oral surgery for prevention of bisphosphonate-related osteonecrosis of the jaw. Oral Surg Oral Med Oral Pathol Oral Radiol 117:e429–e435

    Article  PubMed  Google Scholar 

  7. Agrillo A, Sassano P, Rinna C, Priore P, Iannetti G (2007) Ozone therapy in extractive surgery on patients treated with bisphosphonates. J Craniofac Surg 18:1068–1070

    Article  PubMed  Google Scholar 

  8. Scoletta M, Arata V, Arduino PG, Lerda E, Chiecchio A, Gallesio G, Scully C, Mozzati M (2013) Tooth extractions in intravenous bisphosphonate-treated patients: a refined protocol. J Oral Maxillofac Surg 71:994–999

    Article  PubMed  Google Scholar 

  9. Kan B, Altay MA, Taşar F, Akova M (2011) Low-level laser therapy supported teeth extractions of two patients receiving IV zolendronate. Lasers Med Sci 26:569–575

    Article  PubMed  Google Scholar 

  10. Vescovi P, Meleti M, Merigo E, Manfredi M, Fornaini C, Guidotti R, Nammour S (2013) Case series of 589 tooth extractions in patients under bisphosphonates therapy. Proposal of a clinical protocol supported by Nd:YAG low-level laser therapy. Med Oral Patol Oral Cir Bucal 18:e680–e685

    Article  PubMed  PubMed Central  Google Scholar 

  11. Walsh LJ (1997) The current status of low level laser therapy in dentistry. Part 1. Soft tissue applications. Aust Dent J 42:247–254

    Article  PubMed  CAS  Google Scholar 

  12. Park JB, Ahn S-J, Kang Y-G, Kim E-C, Heo JS, Kang KL (2013) Effects of increased low-level diode laser irradiation time on extraction socket healing in rats. Lasers Med Sci. doi:10.1007/s10103-013-1402-6

    Google Scholar 

  13. Park JJ, Kang KL (2012) Effect of 980-nm GaAlAs diode laser irradiation on healing of extraction sockets in streptozotocin-induced diabetic rats: a pilot study. Lasers Med Sci 27:223–230

    Article  PubMed  Google Scholar 

  14. Kang KL, Chung JH (2009) Effect of low-energy laser irradiation on healing of extraction sockets in ovariectomized rats. Tissue Eng Regen Med 6:1310–1320

    Google Scholar 

  15. Vahtsevanos K, Kyrgidis A, Verrou E, Katodritou E, Triaridis S, Andreadis CG, Boukovinas I, Koloutsos GE, Teleioudis Z, Kitikidou K, Paraskevopoulos P, Zervas K, Antoniades K (2009) Longitudinal cohort study of risk factors in cancer patients of bisphosphonate-related osteonecrosis of the jaw. J Clin Oncol 27:5356–5362

    Article  PubMed  CAS  Google Scholar 

  16. Senel FC, Kadioglu Duman M, Muci E, Cankaya M, Pampu AA, Ersoz S, Gunhan O (2010) Jaw bone changes in rats after treatment with zoledronate and pamidronate. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 109:385–391

    Article  PubMed  Google Scholar 

  17. Kunchur R, Need A, Hughes T, Goss A (2009) Clinical investigation of C-terminal cross-linking telopeptide test in prevention and management of bisphosphonate-associated osteonecrosis of the jaws. J Oral Maxillofac Surg 67:1167–1173

    Article  PubMed  Google Scholar 

  18. Dayisoylu EH, Şenel FÇ, Üngör C, Tosun E, Çankaya M, Ersöz S, Taskesen F (2013) The effects of adjunctive parathyroid hormone injection on bisphosphonate-related osteonecrosis of the jaws: an animal study. Int J Oral Maxillofac Surg 42:1475–1480

    Article  PubMed  CAS  Google Scholar 

  19. Dayisoylu EH, Üngör C, Tosun E, Ersoz S, Kadioglu Duman M, Taskesen F, Senel FC (2014) Does an alkaline environment prevent the development of bisphosphonate-related osteonecrosis of the jaw? An experimental study in rats. Oral Surg Oral Med Oral Pathol Oral Radiol 117:329–334

    Article  PubMed  Google Scholar 

  20. Sonis ST, Watkins BA, Lyng GD, Lerman MA, Anderson KC (2009) Bony changes in the jaws of rats treated with zoledronic acid and dexamethasone before dental extractions mimic bisphosphonate-related osteonecrosis in cancer patients. Oral Oncol 45:164–172

    Article  PubMed  CAS  Google Scholar 

  21. Vescovi P, Merigo E, Meleti M, Fornaini C, Nammour S, Manfredi M (2007) Nd:YAG laser biostimulation of bisphosphonate-associated necrosis of the jawbone with and without surgical treatment. Br J Oral Maxillofac Surg 45:628–632

    Article  PubMed  Google Scholar 

  22. McGee-Lawrence ME, Bradley EW, Dudakovic A, Carlson SW, Ryan ZC, Kumar R, Dadsetan M, Yaszemski MJ, Chen Q, An K-N, Westendorf JJ (2013) Histone deacetylase 3 is required for maintenance of bone mass during aging. Bone 52:296–307

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  23. Karu T (1999) Primary and secondary mechanisms of action of visible to near-IR radiation on cells. J Photochem Photobiol B Biol 49:1–17

    Article  CAS  Google Scholar 

  24. Belletti S, Uggeri J, Mergoni G, Vescovi P, Merigo E, Fornaini C, Nammour S, Manfredi M, Gatti R (2015) Effects of 915 nm GaAs diode laser on mitochondria of human dermal fibroblasts: analysis with confocal microscopy. Lasers Med Sci 30:375–381

    Article  PubMed  Google Scholar 

  25. Neve A, Corrado A, Cantatore FP (2013) Osteocalcin: skeletal and extra-skeletal effects. J Cell Physiol 228:1149–1153

    Article  PubMed  CAS  Google Scholar 

  26. da Silva APRB, Petri AD, Crippa GE, Stuani AS, Stuani AS, Rosa AL, Stuani MBS (2012) Effect of low-level laser therapy after rapid maxillary expansion on proliferation and differentiation of osteoblastic cells. Lasers Med Sci 27:777–783

    Article  PubMed  Google Scholar 

  27. Hirata S, Kitamura C, Fukushima H, Nakamichi I, Abiko Y, Terashita M, Jimi E (2010) Low-level laser irradiation enhances BMP-induced osteoblast differentiation by stimulating the BMP/Smad signaling pathway. J Cell Biochem 111:1445–1452

    Article  PubMed  CAS  Google Scholar 

  28. Pyo S-J, Song W-W, Kim I-R, Park B-S, Kim C-H, Shin S-H, Chung I-K, Kim Y-D (2013) Low-level laser therapy induces the expressions of BMP-2, osteocalcin, and TGF-β1 in hypoxic-cultured human osteoblasts. Lasers Med Sci 28:543–550

    Article  PubMed  Google Scholar 

  29. Theodoro LH, Caiado RC, Longo M, Novaes VCN, Zanini NA, Ervolino E, de Almeida JM, Garcia VG (2014) Effectiveness of the diode laser in the treatment of ligature-induced periodontitis in rats: a histopathological, histometric, and immunohistochemical study. Lasers Med Sci. doi:10.1007/s10103-014-1575-7

    PubMed  Google Scholar 

  30. Marques L, Holgado LA, Francischone LA, **menez JPB, Okamoto R, Kinoshita A (2014) New LLLT protocol to speed up the bone healing process-histometric and immunohistochemical analysis in rat calvarial bone defect. Lasers Med Sci. doi:10.1007/s10103-014-1580-x

    Google Scholar 

  31. de Souza Merli LA, de Medeiros VP, Toma L, Reginato RD, Katchburian E, Nader HB, Faloppa F (2012) The low level laser therapy effect on the remodeling of bone extracellular matrix. Photochem Photobiol 88:1293–1301

    Article  PubMed  Google Scholar 

  32. Sodek J, Ganss B, McKee MD (2000) Osteopontin. Critical Rev Oral Biol Med 11:279–303

    Article  CAS  Google Scholar 

  33. Stein E, Koehn J, Sutter W, Wendtlandt G, Wanschitz F, Thurnher D, Baghestanian M, Turhani D (2008) Initial effects of low-level laser therapy on growth and differentiation of human osteoblast-like cells. Wien Klin Wochenschr 120:112–117

    Article  PubMed  CAS  Google Scholar 

  34. Maruotti N, Corrado A, Neve A, Cantatore FP (2012) Bisphosphonates: effects on osteoblast. Eur J Clin Pharmacol 68:1013–1018

    Article  PubMed  CAS  Google Scholar 

  35. Basso FG, Silveira Turrioni AP, Hebling J, de Souza Costa CA (2013) Zoledronic acid inhibits human osteoblast activities. Gerontology 59:534–541

    Article  PubMed  CAS  Google Scholar 

  36. Corrado A, Neve A, Maruotti N, Gaudio A, Marucci A, Cantatore FP (2010) Dose-dependent metabolic effect of zoledronate on primary human osteoblastic cell cultures. Clin Exp Rheumatol 28:873–879

    PubMed  CAS  Google Scholar 

  37. Shalhoub V, Conlon D, Tassinari M, Quinn C, Partridge N, Stein GS, Lian JB (1992) Glucocorticoids promote development of the osteoblast phenotype by selectively modulating expression of cell growth and differentiation associated genes. J Cell Biochem 50:425–440

    Article  PubMed  CAS  Google Scholar 

  38. López-Jornet P, Camacho-Alonso F, Martínez-Canovas A, Molina-Miñano F, Gómez-García F, Vicente-Ortega V (2011) Perioperative antibiotic regimen in rats treated with pamidronate plus dexamethasone and subjected to dental extraction: a study of the changes in the jaws. J Oral Maxillofac Surg 69:2488–2493

    Article  PubMed  Google Scholar 

  39. Ersan N, van Ruijven LJ, Bronckers ALJJ, Olgaç V, Ilgüy D, Everts V (2014) Teriparatide and the treatment of bisphosphonate-related osteonecrosis of the jaw: a rat model. Dentomaxillofac Radiol 43:20130144

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  40. Kuroshima S, Entezami P, McCauley LK, Yamashita J (2014) Early effects of parathyroid hormone on bisphosphonate/steroid-associated compromised osseous wound healing. Osteoporos Int 25:1141–1150

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  41. Abtahi J, Agholme F, Aspenberg P (2013) Prevention of osteonecrosis of the jaw by mucoperiosteal coverage in a rat model. Int J Oral Maxillofac Surg 42:632–636

    Article  PubMed  CAS  Google Scholar 

  42. Agaçayak KS, Yuksel H, Atilgan S, Koparal M, Uçan MC, Ozgöz M, Yaman F, Atalay Y, Acikan I (2014) Experimental investigation of relationship between trauma and bisphosphonate-related osteonecrosis. Niger J Clin Pract 17:559–564

    Article  PubMed  Google Scholar 

  43. Sarkarat F, Kalantar Motamedi MH, Jahanbani J, Sepehri D, Kahali R, Nematollahi Z (2014) Platelet-Rich Plasma in Treatment of Zoledronic Acid-Induced Bisphosphonate-related Osteonecrosis of the Jaws. Trauma Mon 19:e17196

    Article  PubMed  PubMed Central  Google Scholar 

  44. Jabbour Z, El-Hakim M, Henderson JE, de Albuquerque RF (2014) Bisphosphonates inhibit bone remodeling in the jaw bones of rats and delay healing following tooth extractions. Oral Oncol 50:485–490

    Article  PubMed  CAS  Google Scholar 

  45. Romeo U, Galanakis A, Marias C, Vecchio AD, Tenore G, Palaia G, Vescovi P, Polimeni A (2011) Observation of pain control in patients with bisphosphonate-induced osteonecrosis using low level laser therapy: preliminary results. Photomed Laser Surg 29:447–452

    Article  PubMed  Google Scholar 

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Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Unit of Oral Pathology and Laser-Assisted Oral Surgery, Department of Biomedical, Biotechnological and Translational Sciences, University of Parma, Viale Gramsci 14, 43100, Parma, Italy

    Giovanni Mergoni, Paolo Vescovi, Elisabetta Merigo & Pietro Passerini

  2. Unit of General Pathology, Department of Biomedical, Biotechnological and Translational Sciences, University of Parma, Parma, Italy

    Roberto Sala & Massimiliano G. Bianchi

  3. Unit of Pathology, Department of Biomedical, Biotechnological, and Translational Sciences, University of Parma, Parma, Italy

    Roberta Maestri & Domenico Corradi

  4. Unit of Anatomy Histology and Embryology, Department of Biomedical, Biotechnological and Translational Sciences (S.Bi.Bi.T), University of Parma, Parma, Italy

    Paolo Govoni

  5. Department of Dental Sciences, Faculty of Medicine, University of Liège, Liège, Belgium

    Samir Nammour

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  1. Giovanni Mergoni
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Mergoni, G., Vescovi, P., Sala, R. et al. The effect of laser therapy on the expression of osteocalcin and osteopontin after tooth extraction in rats treated with zoledronate and dexamethasone. Support Care Cancer 24, 807–813 (2016). https://doi.org/10.1007/s00520-015-2847-x

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