| Autor: |
Melo RCO; Departamento de Odontologia, Universidade Federal do Rio Grande do Norte, Natal, RN, Brasil., Martins AA; Departamento de Odontologia, Universidade Federal do Rio Grande do Norte, Natal, RN, Brasil., Vieira GHA; Departamento de Odontologia, Universidade Federal do Rio Grande do Norte, Natal, RN, Brasil., Andrade RVS; Departamento de Odontologia, Universidade Federal do Rio Grande do Norte, Natal, RN, Brasil., Silva DNA; Section of Periodontics, School of Dentistry, University of California, Los Angeles, CA, USA., Chalmers J; Section of Periodontics, School of Dentistry, University of California, Los Angeles, CA, USA., Silveira TM; Section of Periodontics, School of Dentistry, University of California, Los Angeles, CA, USA., Pirih FQ; Section of Periodontics, School of Dentistry, University of California, Los Angeles, CA, USA., Araújo VS; Departamento de Odontologia, Universidade Federal do Rio Grande do Norte, Natal, RN, Brasil., Silva JSP; Departamento de Odontologia, Universidade Federal do Rio Grande do Norte, Natal, RN, Brasil., Lopes MLDS; Departamento de Odontologia, Universidade Federal do Rio Grande do Norte, Natal, RN, Brasil., Leitão RFC; Departamento de Morfologia, Universidade Federal do Ceará, Fortaleza, CE, Brasil., Araújo Júnior RF; Departamento de Morfologia, Universidade Federal do Rio Grande do Norte, Natal, RN, Brasil., Silva ILG; Departamento de Morfologia, Universidade Federal do Rio Grande do Norte, Natal, RN, Brasil., Silva LJT; Departamento de Odontologia, Universidade Federal do Rio Grande do Norte, Natal, RN, Brasil., Barbosa EG; Departamento de Ciências Farmacêuticas, Universidade Federal do Rio Grande do Norte, Natal, RN, Brasil., Araújo AA; Departamento de Biofísica e Farmacologia, Universidade Federal do Rio Grande do Norte, Natal, RN, Brasil. |
| Abstrakt: |
Considering the lack of consensus related to the impact of selective IL-6 receptor inhibition on bone remodeling and the scarcity of reports, especially on large bone defects, this study proposed to evaluate the biological impact of the selective inhibitor of interleukin-6 receptor (tocilizumab) in an experimental model of critical calvarial defect in rats. In this preclinical and in vivo study, 24 male Wistar rats were randomly divided into two groups (n=12/group): defect treated with collagen sponge (CG) and defect treated with collagen sponge associated with 2 mg/kg tocilizumab (TCZ). The defect in the parietal bone was created using an 8-mm diameter trephine drill. After 90 days, the animals were euthanized, and tissue samples (skull caps) were evaluated through micro-CT, histological, immunohistochemistry, cytokines, and RT-qPCR analyses. Tocilizumab reduced mononuclear inflammatory infiltration (P<0.05) and tumor necrosis factor (TNF)-α levels (P<0.01) and down-regulated tissue gene expression of BMP-2 (P<0.001), RUNX-2 (P<0.05), and interleukin (IL)-6 (P<0.05). Moreover, it promoted a stronger immunostaining of cathepsin and RANKL (P<0.05). Micro-CT and histological analyses revealed no impact on general bone formation (P>0.05). The bone cells (osteoblasts, osteoclasts, and osteocytes) in the defect area were similar in both groups (P>0.05). Tocilizumab reduced inflammatory cytokines, decreased osteogenic protein, and increased proteases in a critical bone defect in rats. Ninety days after the local application of tocilizumab in the cranial defect, we did not find a significant formation of bone tissue compared with a collagen sponge. |
