Celecoxib treatment dampens LPS‐induced periapical bone resorption in a mouse model

Abstract

Aim To evaluate the efficacy of selective and nonselective inhibitors of cyclooxygenase‐2 enzymes in the treatment of experimental apical periodontitis induced by bacterial lipopolysaccharide (LPS) in vivo in a mouse model. Methodology Thirty‐six C57BL/6 mice were used. After access cavity preparation, a solution containing E. coli LPS (1.0 µg µL−1) was inoculated into the root canals of the mandibular and maxillary right first molars (n = 72) After 30 days, apical periodontitis was established and the animals were systemically treated with celecoxib, a selective COX‐2 inhibitor (15 mg kg−1), or indomethacin, a nonselective COX‐2 inhibitor (5 mg kg−1), for 7 and 14 days. Blocks containing teeth and bone were removed for histopathological and histometric analyses (haematoxylin and eosin), evaluation of osteoclasts numbers (tartrate‐resistant acid phosphatase enzyme – TRAP) and immunohistochemistry for RANK, RANKL and OPG. Gene expression was performed using reverse transcription and real‐time polymerase chain reaction (qRT‐PCR) for RANK, RANKL, OPG, TRAP, MMP‐9, cathepsin K and calcitonin receptor. Histopathological, histometric, TRAP, immunohistochemistry and qRT‐PCR data were evaluated using Kruskal–Wallis followed by Dunn’s test (α = 0.05). Results Systemic administration of celecoxib for 7 and 14 days prevented periapical bone resorption (P < 0.0001), differently from indomethacin that exacerbated bone resorption at 7 days (P < 0.0001) or exerted no effect at 14 days (P = 0.8488). Celecoxib treatment reduced osteoclast formation in apical periodontitis, regardless of the period of treatment (P < 0.0001 for 7 days and P = 0.026 for 14 days). Administration of celecoxib or indomethacin differentially modulated the expression of genes involved in bone resorption. At 7 days, celecoxib and indomethacin treatment significantly inhibited expression of mRNA for cathepsin K (P = 0.0005 and P = 0.016, respectively) without changing TRAP, MMP‐9 and calcitonin receptor gene expression. At 14 days, celecoxib significantly inhibited expression of mRNA for MMP‐9 (P < 0.0001) and calcitonin receptor (P = 0.004), whilst indomethacin exerted no effect on MMP‐9 (P = 0.216) and calcitonin receptor (P = 0.971) but significantly augmented cathepsin K gene expression (P = 0.001). Conclusions The selective COX‐2 inhibitor celecoxib reduced osteoclastogenic signalling and activity that dampened bone resorption in LPS‐induced apical periodontitis in mice, with greater efficacy than the nonselective inhibitor indomethacin.

Enamel biomineralization under the effects of indomethacin and celecoxib non-steroidal anti-inflammatory drugs

“…For quantification of intensity of the immunostaining in the ameloblast layer, the Software Image J (National Institutes of Health, Bethesda, MD, USA) and the image deconvolution plugin (Color Deconvolution) were used. DAB vector was applied and then the selected channel and threshold were manually adjusted, at 10× magnification 38 . Analysis was carried out by blinded examiners to the sample group assignment at the cervical third of the root, using in 1 section per slide, 1 tooth per animal, from 10 different mice.…”

Systemic inhibition of 5-lipoxygenase by MK-886 exacerbates apical periodontitis bone loss in a mouse model

“…with 10% ketamine hydrochloride (150 mg/kg; National Pharmaceutical Chemistry Union Agener S/A, Embu-Guaçu, SP, Brazil) and xylazine (7.5 mg/kg; Dopaser, Labs Calier S/A, Barcelona, Spain). Anaesthesia was sustained during the operative procedures throughout the experimental period, and the animals were monitored by a veterinarian throughout the entire experimental period as previously described [10,11].…”

“…Conventional glass ionomer cement (S.S. White Dental Articles Ltda, Rio de Janeiro, RJ, Brazil), manipulated according to manufacturer's instructions, was used for restoring the teeth. After LPS inoculation, the animals were kept under supervision for thirty days, in order to establish the apical periodontitis [10].…”

“…The analysis was qualitatively performed by using conventional light microscopy (Zeiss Axio Imager, Carl Zeiss AG Light Microscopy, Göttingen, Germany). For quantitative analysis, the size of apical periodontitis lesions was determined, delineated and measured in mm 2 , on sections representing the largest diameter of the lesion, excluding intact structures (periodontal ligament, cementum and alveolar bone) and including areas of resorption and in ammatory in ltrate, according to previously described parameters [10]. All the analyses were performed using videomicroscopy with the Zeiss AxioVision Software (Carl Zeiss AG Light Microscopy), in conjunction with the AxioCam MRc5 (Carl Zeiss AG Light Microscopy) microscope and camcorder, at 20× magni cation, operated in uorescence mode (excitation at 460-500 nm and emission at 512-542 nm).…”

“…In this sense, considering that AP is a multifactorial disease, to reduce failure in the NSRCT approaches that address microbiology, quality of treatment and host response particularities are needed [7]. Thus, recent research investigate coadjutant therapies to limit the AP development and establishment, or improve their healing rates after NSRCT, with promising results through the use of anti-in ammatory drugs and probiotics via systemic or topical administration, in order to control the in ammatory process during AP establishment and repair [8][9][10][11].…”