Periodontal disease (PD) is a prevalent inflammatory disease with the most severe consequence being the loss of the alveolar bone and teeth. We therefore aimed to evaluate the effects of telmisartan (TELM), an angiotensin II type 1 receptor (Agtr1) antagonist, on the PD-induced alveolar bone loss, in Wistar (W) and Spontaneous Hypertensive Rats (SHRs). PD was induced by ligating the lower first molars with silk, and 10 mg/kg TELM was concomitantly administered for 15 days. The hemimandibles were subjected to microtomography, ELISA was used for detecting tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), CXCL3, and CCL2, while qRT-PCR was used for analyzing expression of components of renin-angiotensin system (RAS) (Agt, Ace, Agt1r, Agt2r, Ace2, and Masr), and bone markers (Runx2, Osx, Catnb, Alp, Col1a1, Opn, Ocn, Bsp, Bmp2, Trap, Rank, Rankl, CtsK, Mmp-2, Mmp-9, and osteoclast-associated receptor (Oscar)). The SHR + PD group showed greater alveolar bone loss than the W + PD group, what was significantly inhibited by treatment with TELM, especially in the SHR group. Additionally, TELM reduced the production of TNF-α, IL-1β, and CXCL3 in the SHR group. The expression of Agt increased in the groups with PD, while Agtr2 reduced, and TELM reduced the expression of Agtr1 and increased the expression of Agtr2, in W and SHRs. PD did not induce major changes in the expression of bone formation markers, except for the expression of Alp, which decreased in the PD groups. The bone resorption markers expression, Mmp9, Ctsk, and Vtn, was higher in the SHR + PD group, compared to the respective control and W + PD group. However, TELM attenuated these changes and increased the expression of Runx2 and Alp. Our study suggested that TELM has a protective effect on the progression of PD, especially in hypertensive animals, as evaluated by the resorption of the lower alveolar bone. This can be partly explained by the modulation in the expression of Angiotensin II receptors (AT1R and AT2R), reduced production of inflammatory mediators, the reduced expression of resorption markers, and the increased expression of the bone formation markers.

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Spontaneously hypertensive rats (SHR) present genetic alterations in bone metabolism and in adaptive immunity. Mast cells (MCs) play a fundamental role in inflammatory response, tissue repair and defense of the organism and may also be involved in the bone metabolism. Thus, in this study we aimed to evaluate the influence of mast cell mediators in the acquisition of the osteogenic phenotype in vitro and in the gene expression of bone markers from calvariae cells of SHR.MethodsPrimary culture from neonatal calvariae obtained by explant technique were expanded and plated in 24‐well culture plates where they received osteogenic medium (OM, ascorbic acid, β‐glycerophosphate and dexamethasone). The RBL‐2H3 MC lines were adapted to osteogenic medium, subsequently stimulated via FcɛRI, and culture supernatant was collected and was added directly into the calvariae culture in concentration of 15%, 10% and 5%. Cell viability was accessed by MTT assay, and gene expression of osteogenic markers was evaluated at day 7 by qRT‐PCR. The protocol was approved by Institutional Animal Care and Use Committees (School of Dentistry of Araçatuba; Process:00490‐2018).ResultsMTT assay did not show a cytotoxic potential from MC supernatant on calvariae culture. MC supernatant, in all concentration, significantly decreased gene expression of the transcription factors Runx2, Osterix, but not β‐catenin. Moreover, it decreased osteocalcin and bone alkaline phosphatase expression, in a dose‐dependent manner. Bone sialoprotein expression was decreased in response to the higher MC supernatant concentration, but the opposite was observed in response to the lower concentration. Osteopontin and type 1 collagen expression were decreased, in a similar manner by all MC supernatant concentrations.ConclusionOur current data allow us to suggest that MC‐derived factors can directly inhibit bone formation‐related markers expression. Further studies are being performed to better understand the mechanisms related to mast cell – bone cell crosstalk.Support or Funding InformationFinancial support and acknowledgments: FAPESP (Grant: #2015/03965‐2 and Grant: #2017/05873‐3)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.