Banca de QUALIFICAÇÃO: ROMULO CAMILO DE OLIVEIRA MELO

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : ROMULO CAMILO DE OLIVEIRA MELO
DATE: 25/09/2025
TIME: 08:30
LOCAL: meet.google.com/odf-vzqu-xdn
TITLE:

EFFECT OF TOCILIZUMAB ON BONE REGENERATION: SELECTIVE INHIBITION OF THE IL-6 RECEPTOR IN CRITICAL BONE DEFECTS

KEY WORDS:

 Interleukin-6; bone regeneration; tocilizumab; critical-size bone defects; inflammation; bone remodeling

PAGES: 60
BIG AREA: Ciências da Saúde
AREA: Odontologia
SUMMARY:

Interleukin-6 (IL-6) plays a biphasic role in bone biology—essential for early repair yet potentially deleterious when chronically elevated, favoring osteoclastogenesis and pathological resorption. Given the lack of consensus on the impact of selective IL-6 receptor (IL-6R) inhibition on bone remodeling and the scarcity of studies in large bone defects, this study evaluated the effect of tocilizumab (TCZ), a selective IL-6R inhibitor, in an experimental rat model of a critical-size calvarial defect. In this in vivo preclinical study, 24 male Wistar rats were randomly assigned to two groups (n = 12/group): a control group (collagen sponge) and a TCZ group (collagen sponge impregnated with 2 mg/kg tocilizumab). An 8-mm critical parietal defect was created in each animal. After 90 days, specimens were analyzed by micro-computed tomography (micro-CT), histology, immunohistochemistry (IHC), ELISA, and RT-qPCR. Tocilizumab significantly reduced mononuclear inflammatory infiltration (P < 0.05) and tumor necrosis factor-alpha levels (TNF-α, P < 0.01). However, downregulation of osteogenic gene markers was observed, including BMP-2 (P < 0.001), RUNX-2 (P < 0.05), and IL-6 (P < 0.05). Additionally, increased immunostaining was detected for markers associated with bone resorption—namely cathepsin and RANKL (P < 0.05). Micro-CT and histologic analyses showed no significant impact on overall bone formation (P > 0.05), with similar counts of osteoblasts, osteoclasts, and osteocytes between groups (P > 0.05). In conclusion, in this rat critical-size defect model, local application of tocilizumab modulated inflammation but did not promote significant new bone formation at 90 days and further signaled resorptive pathways. Future studies are warranted to investigate different doses/concentrations, intervention time windows, and combinations with pro-osteogenic strategies, while considering potential interspecies particularities in the tocilizumab–IL-6R interaction in rodents.

COMMITTEE MEMBERS:
Presidente - 2374605 - AURIGENA ANTUNES DE ARAUJO
Interna - 2644142 - PATRICIA TEIXEIRA DE OLIVEIRA
Externa ao Programa - 2492944 - CAROLINE ADDISON CARVALHO XAVIER DE MEDEIROS - UFRN