Increased bone loss and amount of osteoclasts in kinin B1 receptor knockout mice
Conflict of interest and source of funding statement
This study was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP – Proc. 2008/06676-8). The authors declare that they have no conflict of interests.
João Bosco Pesquero
Universidade Federal de São Paulo
Rua Pedro de Toledo, 669, 9º andar, Vila Clementino, São Paulo-SP 04039-032
The pathophysiology of periodontal diseases involves aspects of immunity and bone remodelling. Considering the role of the kinin B1 receptor (Bdkrb1) in inflammation and healing, the purpose of this study was to evaluate the contribution of Bdkrb1 to the pathogenesis of periodontitis.
Material and Methods
We used a model of ligature-induced experimental periodontitis (LIEP) in mice lacking Bdkrb1 (Bdkrb1−/−) to test the role of this receptor in bone loss and cytokine secretion by lymph nodes cells. Angiotensin-converting enzyme inhibitor (ACEi) was used as a pharmacological strategy to support the genetic model. Also, autonomous effect of Bdkrb1 deletion was evaluated in osteoclasts precursors from bone marrow.
Bdkrb1−/− mice exhibit increased bone loss and IL-17 secretion in response to LIEP when compared to wild type. LIEP does not modify TNF-α, IFN-γ and IL-10 levels in Bdkrb1−/− mice after 21 days. Bone marrow cells from Bdkrb1−/− displayed increased differentiation into functional osteoclasts with consistent artificial calcium phosphate degradation. Furthermore, treatment of mice with ACEi prevented bone destruction.
Bdkrb1 participates in the pathogenesis of LIEP bone loss possibly through mechanisms that involve modulation of the TH17 response, thereby demonstrating its role in the development of periodontitis.