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RETRACTED ARTICLE:Melatonin promotes angiogenesis during repair of bone defects: a radiological and histomorphometric study in rabbit tibiae

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This article was retracted on 03 January 2022

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Abstract

Objectives

The pineal gland hormone, melatonin, is an immunomodulator and neuroendocrine hormone; it also stimulates monocyte, cytokine and fibroblast proliferations, which influence angiogenesis. The aim of this study was to investigate the effects of melatonin on angiogenesis during bone defect repair by means of radiological and histomorphometric evaluations of bone response to melatonin implants.

Materials and methods

Twenty New Zealand rabbits weighing 3,900–4,500 g were used. Twenty melatonin implants were inserted in the proximal metaphyseal area of the animals' right tibia and 20 control areas were located in the left proximal metaphyseal area. Following implantation, the animals were sacrificed in groups of five, after 1, 2, 3 and 4 weeks, respectively. Anteroposterior and lateral radiographs were taken, and radiographic thermal imaging analysis was performed for all groups at different time stages following implant insertion. Samples were sectioned at 5 μm and stained using Hematoxylin–Eosin and Masson's trichrome, supplementing radiographic findings with histomorphometric analysis.

Results

After 4 weeks, radiological images showed complete repair of the bone defects. No healed or residual bone alterations attributable to the presence of the melatonin implant were observed. Histomorphometric analysis at 4 weeks showed the presence of a higher density newly formed bone. There were statistically significant differences in the length of cortical formation between the melatonin group and the control group during the first weeks of the study; there were also statistically significant differences in the number of vessels observed in the melatonin groups at the first two study stages.

Conclusion and clinical relevance

Melatonin may have potential beneficial effects on bone defect repair.

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References

  1. Tan DX, Manchester LC, Terron MP et al (2007) One molecule, many derivatives: a never-ending interaction of melatonin with reactive oxygen and nitrogen species? J Pineal Res 42:28–42

    Article  Google Scholar 

  2. Tan DX, Manchester LC, Reiter RJ et al (1999) Identification of highly elevated levels of melatonin in bone marrow: its origin and significance. Biochim Biophys Acta 1472:206–14

    Article  Google Scholar 

  3. Reiter RJ, Tan DX, Manchester LC et al (2007) Medical implications of melatonin: receptor-mediated and receptor-independent actions. Adv Med Sci 52:11–28

    PubMed  Google Scholar 

  4. Ladizesky MG, Boggio V, Cutrera RA et al (2006) Melatonin effect on bone metabolism in rats treated with methylprednisolone. J Pineal Res 40:297–304

    Article  Google Scholar 

  5. Suzuki N, Somei M, Seki A et al (2008) Novel bromomelatonin derivatives as potentially effective drugs to treat bone diseases. J Pineal Res 45:229–34

    Article  Google Scholar 

  6. Ostrowska Z, Kos-Kudla B, Nowak M et al (2003) The relationship between bone metabolism, melatonin and other hormones in sham-operated and pinealectomized rats. Endocr Regul 37:211–24

    PubMed  Google Scholar 

  7. Calvo-Guirado JL, Gómez-Moreno G, Barone A et al (2009) Melatonin plus porcine bone on discrete calcium deposit implant surface stimulates osteointegration in dental implants. J Pineal Res 47:164–72

    Article  Google Scholar 

  8. Calvo-Guirado JL, Ramírez-Fernández MP, Gómez-Moreno G et al (2010) Melatonin stimulates the growth of new bone around implants in the tibia of rabbits. J Pineal Res 49:356–63

    Article  Google Scholar 

  9. Guardia J, Gómez-Moreno G, Ferrera MJ et al (2009) Evaluation of effects of topic melatonin on implant surface at 5 and 8 weeks in beagle dogs. Clin Implant Dent Relat Res 13:262–8

    Article  Google Scholar 

  10. Muñoz F, López-Peña M, Miño N et al (2009) Topical application of melatonin and growth hormone accelerates bone healing around dental implants in dogs. Clin Implant Dent Relat Res Sep 29. doi:10.1111/j.1708-8208.2009.00242.x

  11. Takechi M, Tatehara S, Satomura K et al (2008) Effect of FGF-2 and melatonin on implant bone healing: a histomorphometric study. J Mater Sci Mater Med 19:2949–52

    Article  Google Scholar 

  12. Nakade O, Koyama H, Ariji H et al (1999) Melatonin stimulates proliferation and type I collagen synthesis in human bone cells in vitro. J Pineal Res 27:106–10

    Article  Google Scholar 

  13. Roth JA, Kim BG, Lin WL et al (1999) Melatonin promotes osteoblast differentiation and bone formation. J Biol Chem 274:22041–7

    Article  Google Scholar 

  14. Cardinali DP, Ladizesky MG, Boggio V et al (2003) Melatonin effects on bone: experimental facts and clinical perspectives. J Pineal Res 34:81–7

    Article  Google Scholar 

  15. Mayo JC, Sainz RM, Tan DX et al (2005) Anti-inflammatory actions of melatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), in macrophages. J Neuroimmunol 165:139–49

    Article  Google Scholar 

  16. Koyama H, Nakade O, Takada Y et al (2002) Melatonin at pharmacologic doses increases bone mass by suppressing resorption through down-regulation of the RANKL-mediated osteoclast formation and activation. J Bone Miner Res 17:1219–29

    Article  Google Scholar 

  17. Ostrowska Z, Ziora K, Kos-Kudła B et al (2010) Melatonin, the RANKL/RANK/OPG system, and bone metabolism in girls with anorexia nervosa. Endokrynol Pol 61:117–23

    PubMed  Google Scholar 

  18. Gómez-Moreno G, Guardia J, Ferrera MJ et al (2010) Melatonin in diseases of the oral cavity. Oral Dis 16:242–7

    Article  Google Scholar 

  19. Korkmaz A, Reiter RJ, Topal T et al (2009) Melatonin: an established antioxidant worthy of use in clinical trials. Mol Med 15:43–50

    Article  Google Scholar 

  20. Cutando A, Gómez-Moreno G, Arana C et al (2007) Melatonin: potential functions in the oral cavity. J Periodontol 78:1094–102

    Article  Google Scholar 

  21. Ganguly K, Sharma AV, Reiter RJ et al (2010) Melatonin promotes angiogenesis during protection and healing of indomethacin-induced gastric ulcer: role of matrix metaloproteinase-2. J Pineal Res 49:130–40

    PubMed  Google Scholar 

  22. Yamada Y, Tamura T, Hariu K et al (2008) Angiogenesis in newly augmented bone observed in rabbit calvarium using a titanium cap. Clin Oral Implants Res 19:1003–9

    Article  Google Scholar 

  23. Soybir G, Topuzlu C, Odabaş O et al (2003) The effects of melatonin on angiogenesis and wound healing. Surg Today 33:896–901

    Article  Google Scholar 

  24. Pugazhenthi K, Kapoor M, Clarkson AN et al (2008) Melatonin accelerates the process of wound repair in full-thickness incisional wounds. J Pineal Res 44:387–96

    Article  Google Scholar 

  25. Street J, Bao M, de Guzman L et al (2002) Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover. Proc Natl Acad Sci USA 99:9656–61

    Article  Google Scholar 

  26. Mayer H, Bertram H, Lindenmaier W et al (2005) Vascular endothelial growth factor (VEGF-A) expression in human mesenchymal stem cells: autocrine and paracrine role on osteoblastic and endothelial differentiation. J Cell Biochem 95:827–39

    Article  Google Scholar 

  27. Dai J, Rabie AB (2007) VEGF: an essential mediator of both angiogenesis and endochondral ossification. J Dent Res 86:937–50

    Article  Google Scholar 

  28. Shi ZB, Wang KZ (2010) Effects of recombinant adeno-associated viral vectors on angiopoiesis and osteogenesis in cultured rabbit bone marrow stem cells via co-expressing hVEGF and hBMP genes: a preliminary study in vitro. Tissue Cell 42:314–21

    Article  Google Scholar 

  29. Das R, Jahr H, van Osch GJ et al (2010) The role of hypoxia in bone marrow-derived mesenchymal stem cells: considerations for regenerative medicine approaches. Tissue Eng Part B Rev 16:159–168

    Article  Google Scholar 

  30. Mias C, Trouche E, Seguelas MH et al (2008) Ex vivo pretreatment with melatonin improves survival, proangiogenic/mitogenic activity, and efficiency of mesenchymal stem cells injected into ischemic kidney. Stem Cells 26:1749–57

    Article  Google Scholar 

  31. Dai M, Cui P, Yu M et al (2008) Melatonin modulates the expression of VEGF and HIF-1 alpha induced by CoCl2 in cultured cancer cells. J Pineal Res 44:121–6

    Article  Google Scholar 

  32. Mediavilla MD, Sanchez-Barcelo EJ, Tan DX et al (2010) Basic mechanisms involved in the anti-cancer effects of melatonin. Curr Med Chem 17:4462–81

    Article  Google Scholar 

  33. Park SY, Jang WJ, Yi EY et al (2010) Melatonin suppresses tumor angiogenesis by inhibiting HIF-1alpha stabilization under hypoxia. J Pineal Res 48:178–84

    Article  Google Scholar 

  34. Cui P, Luo Z, Zhang H et al (2006) Effect and mechanism of melatonin's action on the proliferation of human umbilical vein endothelial cells. J Pineal Res 41:358–62

    Article  Google Scholar 

  35. Pandi-Perumal SR, Srinivasan V, Maestroni GJ et al (2006) Melatonin: nature's most versatile biological signal? FEBS J 273:2813–38

    Article  Google Scholar 

Download references

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Authors and Affiliations

  1. Department of Implant Dentistry, Faculty of Medicine and Dentistry, University of Murcia, Murcia, Spain

    María Piedad Ramírez-Fernández, José Luis Calvo-Guirado, Bruno Negri, Guillermo Pardo-Zamora & Jose Manuel Granero

  2. Department of Restorative Dentistry, Faculty of Medicine and Dentistry, University of Murcia, Murcia, Spain

    José Eduardo-Maté Sánchez de-Val & Rafael Arcesio Delgado-Ruiz

  3. Master of Oral Surgery and Implantology, University of Valencia, Valencia, Spain

    David Peñarrocha

  4. Department of Oral Surgery, the Complutense University of Madrid, Madrid, Spain

    Cristina Barona

  5. Department of Radiology and Physical Medicine, Faculty of Medicine and Dentistry, University of Murcia, Murcia, Spain

    Miguel Alcaraz-Baños

  6. Hospital Morales Meseguer, Marqués de los Vélez, s/n, 30008, Murcia, Spain

    María Piedad Ramírez-Fernández

Authors
  1. María Piedad Ramírez-Fernández
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  2. José Luis Calvo-Guirado
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  3. José Eduardo-Maté Sánchez de-Val
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  4. Rafael Arcesio Delgado-Ruiz
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  5. Bruno Negri
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  6. Guillermo Pardo-Zamora
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  7. David Peñarrocha
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  8. Cristina Barona
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  9. Jose Manuel Granero
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  10. Miguel Alcaraz-Baños
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Corresponding author

Correspondence to María Piedad Ramírez-Fernández.

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Ramírez-Fernández, M.P., Calvo-Guirado, J.L., de-Val, J.EM.S. et al. RETRACTED ARTICLE:Melatonin promotes angiogenesis during repair of bone defects: a radiological and histomorphometric study in rabbit tibiae. Clin Oral Invest 17, 147–158 (2013). https://doi.org/10.1007/s00784-012-0684-6

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  • DOI: https://doi.org/10.1007/s00784-012-0684-6

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