ORIGINAL ARTICLE Effects of immunosuppressant FK-506 on tooth movement RL Santos MLF de Farias LMC de Mendonc ¸a RT Gonc ¸alves MA Martins MMG de Souza Authors' affiliations: R.L. Santos, Specialist in Orthodontics at the Federal University of Alfenas, Minas Gerais and Master in Orthodontics at the Federal University of Rio de Janeiro, Brazil M.L.F. de Farias, Doctor in Endocrinology at the Federal University of Rio de Janeiro and Adjunct Professor of Endocrinology at the Federal University of Rio de Janeiro, Brazil L.M.C. de Mendonc ¸a, Rheumatologist physician at the Federal University of Rio de Janeiro and responsible for the Osteometabolic Disease Outpatient Clinic of the Clemente Fraga Filho University Hospital, Rio de Janeiro, Brazil R.T. Gonc ¸alves, Nephrologist physician in the Department of Nephrology and responsible for the Renal Transplantation Unit of the Clemente Fraga Filho University Hospital, Rio de Janeiro, Brazil M.A. Martins, Doctor in Cell and Molecular Biology at the Oswaldo Cruz Foudation – Fiocruz, Rio de Janeiro, Brazil and Post-doctorate at the William Harvey Research Institute and Imperial College, London, UK and Chief of the Inflammation Laboratory of the Oswaldo Cruz Foudation, Rio de Janeiro, Brazil M.M.G. de Souza, Master and Doctor in Orthodontics at the Federal University of Rio de Janeiro and Adjunct Professor in the Department of Paediatric Dentistry and Orthodontics at the Federal University of Rio de Janeiro, Brazil Correspondence to: Roge ´rio Lacerda Santos Rua Ipatinga, 170, Planalto Divino ´polis- MG- Brazil CEP: 35501-191 E-mail: lacerdaorto@hotmail.com or lacerdaorto@bol.com.br Structured Abstract Authors – Santos RL, de Farias MLF, de Mendonc ¸a LMC, Gonc ¸ alves RT, Martins MA, de Souza MMG Objective – To test the hypothesis that immunosuppressant tacrolimus treatment can interfere with bone turnover and rate of tooth movement. Material and Methods – One-hundred twenty Wistar male rats were divided into four groups: Group 1 (rats subjected to orthodontic movement plus treatment with saline solution vehicle), Group 2 (rats subjected to orthodontic movement plus treatment with FK506), Group 3 (rats treated with FK506 only), and Group 4 (rats treated with saline solution vehicle). The maxillary incisors were laterally moved with a reciprocal load of 35 cN. The dosage of FK506 was 2 mg ⁄ kg ⁄ day. HowshipÕs lacunae, osteoclasts, and macrophages were counted. Results – Tooth movement was found to be greater in Group 1 than in Group 2 for all time periods (on days 3, 7, and 14), although a significant difference was observed only on days 7 and 14 (p < 0.05). The number of osteoclasts was smaller in Group 1 than in Group 2, whereas the number of HowshipÕs lacunae was greater. Conclusion – FK506 has the capacity of promoting osteoclasts inhibition with probable osteoclastic apoptosis of alveolar bone following tooth movement. Key words: bone; immunosuppressant; orthodontics; tooth movement Introduction Tacrolimus (FK506) is an immunosuppressive agent derived from Strep- tomyces tsukubaensis (1), being widely used in patients submitted to organ transplantation (2). Some authors (3, 4) have suggested that FK506 exerts its anti-inflammatory effect mainly by interfering with the activation of T cells, suppressing the production of cytokines, particularly TNF-a, IL-1b, IL-2, and IL6, modulating the inflammation, and decreasing both tissue destruction and bone resorption. On the other hand, bone turnover and development of severe osteoporosis have been reported (5). Studies using cell culture (6, 7) have demonstrated that not only mes- senger RNAs of NFATc1, NFATc2 and NFATc3, essential transcription factors for osteoclastic differentiation are present in the osteoclast-pre- cursor cells, but also that FK506 inhibits the final phases of cell life cycle through osteoclastic apoptosis. As a whole, these findings are in accor- dance with the idea that the mechanisms by which osteoclastogenesis is Dates: Accepted 20 March 2010 To cite this article: Santos RL, de Farias MLF, de Mendonc ¸a LMC, Gonc ¸alves RT, Martins MA, de Souza MMG: Effects of immunosuppressant FK-506 on tooth movement Orthod Craniofac Res 2010;13:153–161 Copyright Ó 2010 The Authors Journal compilation Ó 2010 Blackwell Munksgaard