Chronic treatment with zoledronic acid alters the expression levels of inflammatory, bone and apoptotic markers and toll-like receptors 2 and 4 in rat dental pulp.

Publication date: Available online 6 February 2019

Source: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology

Author(s): Paulo Goberlânio de Barros Silva, Antonio Ernando Carlos Ferreira, Camila Carvalho de Oliveira, Maria Elisa Quesado Lima Verde, Milena Oliveira Freitas, Fabrício Bitu Sousa, Mário Rogério Lima Mota, Ana Paula Negreiros Nunes Alves

Abstract

Objective

To evaluate the immunostaining of inflammatory, apoptotic and bone markers and the toll-like-receptors (TLR) 2 and 4 in dental pulp from rats treated with zoledronic acid (ZA).

Study Design

We administered four intravascular infusions of saline (control group) or 0.20 mg.kg⁻¹ ZA in Wistar rats (n=6/group). After 70 days the three rights molars (n=18/group) were microscopically evaluated (presence of ectasic/dilated blood vessels and inflammatory cells). Immunohistochemistry was performed for TRAP (cell counting), COX-2, IL-6, TLR2, TLR4, RANKL, OPG and caspase-3 (scored (0-3) in odontoblast and non-odontoblast dental pulp cells). The Mann-Whitney and Fisher's exact tests and Spearman correlation were used (GraphPadPrism 5.0).

Results

There was no alteration in ectasic/dilated blood vessels (p=0.101) or inflammatory cells (p=0.500), but the number of TRAP-positive cells was reduced in the ZA-group (p=0.027). In ZA-group odontoblasts, immunostaining for COX-2 (p=0.044), TLR4 (p=0.003), OPG (p=0.035) and caspase-3 (p=0.039) increased and RANKL (p=0.045) reduced. In non-odontoblast dental pulp cells, RANKL immunostaining reduced (p=0.009). In ZA-group RANKL/OPG ratio reduced in odontoblast (p=0.022) and non-odontoblast dental pulp cells (p=0.007). IL-6 did not differ between groups.

Conclusions

ZA increases the expression levels of inflammatory, apoptotic markers and TLR4 and alters bone makers in the dental pulp of rats.

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