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Effect of IL-2 inhibition by FK-506 on RANKL and OPG gene expression in ligature-induced periodontal disease: an in vitro and in vivo study

Grant number: 05/04428-9
Support Opportunities:Regular Research Grants
Duration: May 01, 2006 - April 30, 2008
Field of knowledge:Health Sciences - Dentistry - Periodontology
Principal Investigator:Carlos Rossa Junior
Grantee:Carlos Rossa Junior
Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil


The last few decades have witnessed a great progress in the understanding of the events controlling the immune system. Also, the development of drugs presenting allegedly selective effects enable the modulation of the immune response allowing a controlled immunosuppression. Tacrolimus (FK506) is an immunosuppressive drug used to prevent rejection of transplanted organs. Its immunosuppressive activity is reported to be 100 times more potent than that of cyclosporin. FK506 interacts with a Calcium-dependent protein called cyclophilin which inhibits the activity of calcioneurin and impairs Calcium-dependent events. The consequence of this modulation of Calcium-dependent events is the transcriptional inhibition of IL-2 expression, resulting in a potent decrease on proliferation of T cells as well as reducing cytokine synthesis by CD4+ lymphocytes. Information of the effects of FK506 on bone tissue are both controversial and inconclusive, ranging from exacerbation of bone resorption to favoring bone metabolism and osteoblast differentiation. The understanding of the regulation of bone remodelling proccess had a major breakthrough in the last few years represented by the identification of a new cytokine system that constitutes the current paradigm in bone biology. This cytokine system ioncludes proteins RANKL (receptor activator of nuclear factor kappa-B) and OPG (osteoprotegerin). Interaction of RANKl with its receptor RANK has been shown to be both necessary and sufficient for osteoclastogenesis and increased osteoclast activity, whereas OPG acts as a soluble decoy receptor blocking/minimizing interaction of RANKL and RANK, thereby preventing its biological effects. We have recently found that administration of FK506 to rats with experimentally induced periodontal disease resulted not only in the inhibition of the inflammatory proccess, but also a significant decrease on the alveolar bone resorption. Based on the controversial results of the effects of FK506 on bone resorption and also on lack of information regarding regulation of RANKL and OPG expression by FK506, this project has the purpose of evaluating both in vitro and in vivo the effets of FK506 on expression of RANKL and OPG. The main hypothesis is that FK506 does have a specific role on the modulation of RANKL and OPG. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DE AQUINO, SABRINA GARCIA; GUIMARAES, MORGANA RODRIGUES; STACH-MACHADO, DAGMAR RUTH; FRANCISCO DA SILVA, JULIETE APARECIDA; SPOLIDORIO, LUIS CARLOS; ROSSA, JR., CARLOS. Differential regulation of MMP-13 expression in two models of experimentally induced periodontal disease in rats. ARCHIVES OF ORAL BIOLOGY, v. 54, n. 7, p. 609-617, . (06/07283-4, 05/04428-9)
DE AQUINO, SABRINA GARCIA; MANZOLLI LEITE, FABIO RENATO; STACH-MACHADO, DAGMAR RUTH; FRANCISCO DA SILVA, JULIETE APARECIDA; SPOLIDORIO, LUIS CARLOS; ROSSA, JR., CARLOS. Signaling pathways associated with the expression of inflammatory mediators activated during the course of two models of experimental periodontitis. Life Sciences, v. 84, n. 21-22, p. 745-754, . (06/07283-4, 05/04428-9)

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