Skip to main content
Erschienen in: Clinical Oral Investigations 1/2013

01.01.2013 | Original Article

RETRACTED ARTICLE:Melatonin promotes angiogenesis during repair of bone defects: a radiological and histomorphometric study in rabbit tibiae

verfasst von: María Piedad Ramírez-Fernández, José Luis Calvo-Guirado, José Eduardo-Maté Sánchez de-Val, Rafael Arcesio Delgado-Ruiz, Bruno Negri, Guillermo Pardo-Zamora, David Peñarrocha, Cristina Barona, Jose Manuel Granero, Miguel Alcaraz-Baños

Erschienen in: Clinical Oral Investigations | Ausgabe 1/2013

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat 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 42:28–42CrossRef 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 42:28–42CrossRef
2.
Zurück zum Zitat 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 1472:206–14CrossRef 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 1472:206–14CrossRef
3.
Zurück zum Zitat Reiter RJ, Tan DX, Manchester LC et al (2007) Medical implications of melatonin: receptor-mediated and receptor-independent actions. Adv Med Sci 52:11–28PubMed Reiter RJ, Tan DX, Manchester LC et al (2007) Medical implications of melatonin: receptor-mediated and receptor-independent actions. Adv Med Sci 52:11–28PubMed
4.
Zurück zum Zitat Ladizesky MG, Boggio V, Cutrera RA et al (2006) Melatonin effect on bone metabolism in rats treated with methylprednisolone. J Pineal Res 40:297–304CrossRef Ladizesky MG, Boggio V, Cutrera RA et al (2006) Melatonin effect on bone metabolism in rats treated with methylprednisolone. J Pineal Res 40:297–304CrossRef
5.
Zurück zum Zitat Suzuki N, Somei M, Seki A et al (2008) Novel bromomelatonin derivatives as potentially effective drugs to treat bone diseases. J Pineal Res 45:229–34CrossRef Suzuki N, Somei M, Seki A et al (2008) Novel bromomelatonin derivatives as potentially effective drugs to treat bone diseases. J Pineal Res 45:229–34CrossRef
6.
Zurück zum Zitat 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 37:211–24PubMed 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 37:211–24PubMed
7.
Zurück zum Zitat 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 47:164–72CrossRef 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 47:164–72CrossRef
8.
Zurück zum Zitat 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 49:356–63CrossRef 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 49:356–63CrossRef
9.
Zurück zum Zitat 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 13:262–8CrossRef 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 13:262–8CrossRef
10.
11.
Zurück zum Zitat 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 19:2949–52CrossRef 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 19:2949–52CrossRef
12.
Zurück zum Zitat 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 27:106–10CrossRef 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 27:106–10CrossRef
13.
Zurück zum Zitat Roth JA, Kim BG, Lin WL et al (1999) Melatonin promotes osteoblast differentiation and bone formation. J Biol Chem 274:22041–7CrossRef Roth JA, Kim BG, Lin WL et al (1999) Melatonin promotes osteoblast differentiation and bone formation. J Biol Chem 274:22041–7CrossRef
14.
Zurück zum Zitat Cardinali DP, Ladizesky MG, Boggio V et al (2003) Melatonin effects on bone: experimental facts and clinical perspectives. J Pineal Res 34:81–7CrossRef Cardinali DP, Ladizesky MG, Boggio V et al (2003) Melatonin effects on bone: experimental facts and clinical perspectives. J Pineal Res 34:81–7CrossRef
15.
Zurück zum Zitat 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 165:139–49CrossRef 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 165:139–49CrossRef
16.
Zurück zum Zitat 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 17:1219–29CrossRef 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 17:1219–29CrossRef
17.
Zurück zum Zitat 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 61:117–23PubMed 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 61:117–23PubMed
18.
Zurück zum Zitat Gómez-Moreno G, Guardia J, Ferrera MJ et al (2010) Melatonin in diseases of the oral cavity. Oral Dis 16:242–7CrossRef Gómez-Moreno G, Guardia J, Ferrera MJ et al (2010) Melatonin in diseases of the oral cavity. Oral Dis 16:242–7CrossRef
19.
Zurück zum Zitat Korkmaz A, Reiter RJ, Topal T et al (2009) Melatonin: an established antioxidant worthy of use in clinical trials. Mol Med 15:43–50CrossRef Korkmaz A, Reiter RJ, Topal T et al (2009) Melatonin: an established antioxidant worthy of use in clinical trials. Mol Med 15:43–50CrossRef
20.
Zurück zum Zitat Cutando A, Gómez-Moreno G, Arana C et al (2007) Melatonin: potential functions in the oral cavity. J Periodontol 78:1094–102CrossRef Cutando A, Gómez-Moreno G, Arana C et al (2007) Melatonin: potential functions in the oral cavity. J Periodontol 78:1094–102CrossRef
21.
Zurück zum Zitat 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 49:130–40PubMed 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 49:130–40PubMed
22.
Zurück zum Zitat 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 19:1003–9CrossRef 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 19:1003–9CrossRef
23.
Zurück zum Zitat Soybir G, Topuzlu C, Odabaş O et al (2003) The effects of melatonin on angiogenesis and wound healing. Surg Today 33:896–901CrossRef Soybir G, Topuzlu C, Odabaş O et al (2003) The effects of melatonin on angiogenesis and wound healing. Surg Today 33:896–901CrossRef
24.
Zurück zum Zitat Pugazhenthi K, Kapoor M, Clarkson AN et al (2008) Melatonin accelerates the process of wound repair in full-thickness incisional wounds. J Pineal Res 44:387–96CrossRef Pugazhenthi K, Kapoor M, Clarkson AN et al (2008) Melatonin accelerates the process of wound repair in full-thickness incisional wounds. J Pineal Res 44:387–96CrossRef
25.
Zurück zum Zitat 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 99:9656–61CrossRef 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 99:9656–61CrossRef
26.
Zurück zum Zitat 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 95:827–39CrossRef 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 95:827–39CrossRef
27.
Zurück zum Zitat Dai J, Rabie AB (2007) VEGF: an essential mediator of both angiogenesis and endochondral ossification. J Dent Res 86:937–50CrossRef Dai J, Rabie AB (2007) VEGF: an essential mediator of both angiogenesis and endochondral ossification. J Dent Res 86:937–50CrossRef
28.
Zurück zum Zitat 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 42:314–21CrossRef 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 42:314–21CrossRef
29.
Zurück zum Zitat 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 16:159–168CrossRef 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 16:159–168CrossRef
30.
Zurück zum Zitat 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 26:1749–57CrossRef 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 26:1749–57CrossRef
31.
Zurück zum Zitat 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 44:121–6CrossRef 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 44:121–6CrossRef
32.
Zurück zum Zitat Mediavilla MD, Sanchez-Barcelo EJ, Tan DX et al (2010) Basic mechanisms involved in the anti-cancer effects of melatonin. Curr Med Chem 17:4462–81CrossRef Mediavilla MD, Sanchez-Barcelo EJ, Tan DX et al (2010) Basic mechanisms involved in the anti-cancer effects of melatonin. Curr Med Chem 17:4462–81CrossRef
33.
Zurück zum Zitat Park SY, Jang WJ, Yi EY et al (2010) Melatonin suppresses tumor angiogenesis by inhibiting HIF-1alpha stabilization under hypoxia. J Pineal Res 48:178–84CrossRef Park SY, Jang WJ, Yi EY et al (2010) Melatonin suppresses tumor angiogenesis by inhibiting HIF-1alpha stabilization under hypoxia. J Pineal Res 48:178–84CrossRef
34.
Zurück zum Zitat 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 41:358–62CrossRef 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 41:358–62CrossRef
35.
Zurück zum Zitat Pandi-Perumal SR, Srinivasan V, Maestroni GJ et al (2006) Melatonin: nature's most versatile biological signal? FEBS J 273:2813–38CrossRef Pandi-Perumal SR, Srinivasan V, Maestroni GJ et al (2006) Melatonin: nature's most versatile biological signal? FEBS J 273:2813–38CrossRef
Metadaten
Titel
RETRACTED ARTICLE:Melatonin promotes angiogenesis during repair of bone defects: a radiological and histomorphometric study in rabbit tibiae
verfasst von
María Piedad Ramírez-Fernández
José Luis Calvo-Guirado
José Eduardo-Maté Sánchez de-Val
Rafael Arcesio Delgado-Ruiz
Bruno Negri
Guillermo Pardo-Zamora
David Peñarrocha
Cristina Barona
Jose Manuel Granero
Miguel Alcaraz-Baños
Publikationsdatum
01.01.2013
Verlag
Springer Berlin Heidelberg
Erschienen in
Clinical Oral Investigations / Ausgabe 1/2013
Print ISSN: 1432-6981
Elektronische ISSN: 1436-3771
DOI
https://doi.org/10.1007/s00784-012-0684-6

Weitere Artikel der Ausgabe 1/2013

Clinical Oral Investigations 1/2013 Zur Ausgabe

Parodontalbehandlung verbessert Prognose bei Katheterablation

19.04.2024 Vorhofflimmern Nachrichten

Werden Personen mit Vorhofflimmern in der Blanking-Periode nach einer Katheterablation gegen eine bestehende Parodontitis behandelt, verbessert dies die Erfolgsaussichten. Dafür sprechen die Resultate einer prospektiven Untersuchung.

Invasive Zahnbehandlung: Wann eine Antibiotikaprophylaxe vor infektiöser Endokarditis schützt

11.04.2024 Endokarditis Nachrichten

Bei welchen Personen eine Antibiotikaprophylaxe zur Prävention einer infektiösen Endokarditis nach invasiven zahnärztlichen Eingriffen sinnvoll ist, wird diskutiert. Neue Daten stehen im Einklang mit den europäischen Leitlinienempfehlungen.

Zell-Organisatoren unter Druck: Mechanismen des embryonalen Zahnwachstums aufgedeckt

08.04.2024 Zahnmedizin Nachrichten

Der Aufbau von Geweben und Organen während der Embryonalentwicklung wird von den Zellen bemerkenswert choreografiert. Für diesen Prozess braucht es spezielle sogenannte „Organisatoren“. In einer aktuellen Veröffentlichung im Fachjournal Nature Cell Biology berichten Forschende durch welchen Vorgang diese Organisatoren im Gewebe entstehen und wie sie dann die Bildung von Zähnen orchestrieren.

Die Oralprophylaxe & Kinderzahnheilkunde umbenannt

11.03.2024 Kinderzahnmedizin Nachrichten

Infolge der Umbenennung der Deutschen Gesellschaft für Kinderzahnheilkunde in Deutsche Gesellschaft für Kinderzahnmedizin (DGKiZ) wird deren Mitgliederzeitschrift Oralprophylaxe & Kinderzahnheilkunde in Oralprophylaxe & Kinderzahnmedizin umbenannt. Aus diesem Grunde trägt die erste Ausgabe in 2024 erstmalig den neuen Titel.

Newsletter

Bestellen Sie unseren kostenlosen Newsletter Update Zahnmedizin und bleiben Sie gut informiert – ganz bequem per eMail.