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.

Author

Paulo Goberlânio de Barros Silva

Affiliation

Department of Dental Clinic, Division of Oral Pathology, Faculty of Pharmacy, Dentistry and Nursing, Federal University of Ceará, Fortaleza, Ceará, Brazil; Department of Dentistry, Unichristus, Fortaleza, Ceará, Brazil; Ceará Oncology School, Ceará Cancer Institute, Hospital Haroldo Juaçaba, Fortaleza, Ceará, Brazil. Electronic address: [Email]

Abstract

OBJECTIVE : The aim of this study was to evaluate the immunostaining of inflammatory, apoptotic, and bone markers, as well as Toll-like-receptors (TLRs) 2 and 4 in the dental pulp in rats treated with zoledronic acid (ZA).
METHODS : We administered 4 intravascular infusions of saline (control group) or 0.20 mg.kg-1 ZA in Wistar rats (n = 6/group). After 70 days, the 3 rights molars (n = 18/group) were microscopically evaluated (presence of ectasic/dilated blood vessels and inflammatory cells). Immunohistochemistry was performed for tartrate resistant acid phosphatase 5 (TRAP; cell counting), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), TLR2, TLR4, receptor activator of nuclear kappa B ligand (RANKL), osteoprotegerin (OPG), and caspase-3 (scored 0-3 in odontoblast and nonodontoblast dental pulp cells). Mann-Whitney and Fisher's exact tests and Spearman's correlation were used (GraphPad Prism 5.0).
RESULTS : There was no alteration in ectasic/dilated blood vessels (P = .101) or inflammatory cells (P = .500), but the number of TRAP-positive cells was reduced in the ZA-group (P = .027). In ZA-group odontoblasts, immunostaining for COX-2 (P = .044), TLR4 (P = .003), OPG (P = .035) and caspase-3 (P = .039) increased, and that for RANKL (P = 0.045) decreased. In nonodontoblast dental pulp cells, RANKL immunostaining decreased (P = .009). In the ZA group, the RANKL/OPG ratio decreased in odontoblast (P = .022) and nonodontoblast dental pulp cells (P = .007). IL-6 did not differ between the groups.
CONCLUSIONS : ZA increases the expression levels of inflammatory, apoptotic markers, and TLR4 and alters bone makers in the dental pulp of rats.

OUR Recent Articles