Periapical bone response to bacterial lipopolysaccharide is shifted upon cyclooxygenase blockage

Ribeiro-Santos, Fernanda Regina; Silva, Geyson Galo da; Petean, Igor Bassi Ferreira; Arnez, Maya Fernanda Manfrin; Silva, Léa Assed Bezerra da; Faccioli, Lúcia Helena; Paula-Silva, Francisco Wanderley Garcia

doi:10.1590/1678-7757-2018-0641

Cited by 16 publications

(19 citation statements)

References 31 publications

(45 reference statements)

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“…Thus, this study used 30 days after inoculation of LPS, which means that apical periodontitis was established prior to the treatment with NSAIDs. The protocol of treatment, that is time and drug concentration, was performed according to a previous study (Ribeiro-Santos et al 2019). Because indomethacin is a nonselective COX-2 inhibitor, long-term use of this medication should be considered regarding side effects.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, meloxicam could provide more benefit in the treatment of human apical periodontitis than nonselective COX-2 inhibitors, since it has similar efficacy and less gastric damage than indomethacin. In the present study, indomethacin was used due to the fact that it is a classic NSAID drug, used in most studies and has been used in previous studies to investigate experimentally induced apical periodontitis, thus making it possible to compare the results obtained (Oguntebi et al 1989;Ribeiro-Santos et al 2019).…”

Section: Discussionmentioning

confidence: 99%

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

Petean¹,

Almeida-Júnior²,

Arnez³

et al. 2021

Int Endodontic J

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Petean¹,

Almeida-Júnior²,

Arnez³

et al. 2021

Int Endodontic J

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“…Advances have been made in understanding the pathogenesis of AP, especially the identification of cells and mediators capable of modulating the immune system. The dynamic balance between the protective effect of inflammation and its destructive capabilities is an active field of investigation that includes immunotherapy [ 45 – 47 ], antioxidants [ 48 – 59 ], selective estrogen receptor modulators [ 60 , 61 ], stem cells [ 62 – 66 ], phototherapy [ 67 – 71 ], matrix metalloproteinase inhibitors [ 72 , 73 ], anti-inflammatory agents [ 74 – 77 ], and SPMs [ 78 – 81 ].…”

Section: Main Textmentioning

confidence: 99%

Specialized pro-resolving lipid mediators in endodontics: a narrative review

et al. 2021

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Endodontics is the branch of dentistry concerned with the morphology, physiology, and pathology of the human dental pulp and periradicular tissues. Human dental pulp is a highly dynamic tissue equipped with a network of resident immunocompetent cells that play major roles in the defense against pathogens and during tissue injury. However, the efficiency of these mechanisms during dental pulp inflammation (pulpitis) varies due to anatomical and physiological restrictions. Uncontrolled, excessive, or unresolved inflammation can lead to pulp tissue necrosis and subsequent bone infections called apical periodontitis. In most cases, pulpitis treatment consists of total pulp removal. Although this strategy has a good success rate, this treatment has some drawbacks (lack of defense mechanisms, loss of healing capacities, incomplete formation of the root in young patients). In a sizeable number of clinical situations, the decision to perform pulp extirpation and endodontic treatment is justifiable by the lack of therapeutic tools that could otherwise limit the immune/inflammatory process. In the past few decades, many studies have demonstrated that the resolution of acute inflammation is necessary to avoid the development of chronic inflammation and to promote repair or regeneration. This active process is orchestrated by Specialized Pro-resolving lipid Mediators (SPMs), including lipoxins, resolvins, protectins and maresins. Interestingly, SPMs do not have direct anti-inflammatory effects by inhibiting or directly blocking this process but can actively reduce neutrophil infiltration into inflamed tissues, enhance efferocytosis and bacterial phagocytosis by monocytes and macrophages and simultaneously inhibit inflammatory cytokine production. Experimental clinical application of SPMs has shown promising result in a wide range of inflammatory diseases, such as renal fibrosis, cerebral ischemia, marginal periodontitis, and cancer; the potential of SPMs in endodontic therapy has recently been explored. In this review, our objective was to analyze the involvement and potential use of SPMs in endodontic therapies with an emphasis on SPM delivery systems to effectively administer SPMs into the dental pulp space.

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“…Clinically, short-term ibuprofen treatment does not impair post-tooth extraction bone repair or is detrimental to dental implant osseointegration 48 . Recent studies even indicate NSAIDs can inhibit periodontal osteoclast activation following bacterial lipopolysaccharide-induced inflammation 49 . The effects of NSAIDs in bone repair need to be better defined 50 , in particular the potential positive effects of NSAID administration may be beneficial in chronic pathological situations such as long-term bacterial infection, chronic stress, and chronic force.…”

Section: Smoc2 Is Required For Bone Repair and During Periodontal Agingmentioning

confidence: 99%

Deficiency of the SMOC2 matricellular protein impairs bone healing and produces age-dependent bone loss

Morkmued¹,

Clauss²,

Schuhbaur³

et al. 2020

Sci Rep

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Secreted extracellular matrix components which regulate craniofacial development could be reactivated and play roles in adult wound healing. We report a patient with a loss-of-function of the secreted matricellular protein SMOC2 (SPARC related modular calcium binding 2) presenting severe oligodontia, microdontia, tooth root deficiencies, alveolar bone hypoplasia, and a range of skeletal malformations. Turning to a mouse model, Smoc2-GFP reporter expression indicates SMOC2 dynamically marks a range of dental and bone progenitors. While germline Smoc2 homozygous mutants are viable, tooth number anomalies, reduced tooth size, altered enamel prism patterning, and spontaneous age-induced periodontal bone and root loss are observed in this mouse model. Whole-genome RNA-sequencing analysis of embryonic day (E) 14.5 cap stage molars revealed reductions in early expressed enamel matrix components (Odontogenic ameloblast-associated protein) and dentin dysplasia targets (Dentin matrix acidic phosphoprotein 1). We tested if like other matricellular proteins SMOC2 was required for regenerative repair. We found that the Smoc2-GFP reporter was reactivated in adjacent periodontal tissues 4 days after tooth avulsion injury. Following maxillary tooth injury, Smoc2−/− mutants had increased osteoclast activity and bone resorption surrounding the extracted molar. Interestingly, a 10-day treatment with the cyclooxygenase 2 (COX2) inhibitor ibuprofen (30 mg/kg body weight) blocked tooth injury-induced bone loss in Smoc2−/− mutants, reducing matrix metalloprotease (Mmp)9. Collectively, our results indicate that endogenous SMOC2 blocks injury-induced jaw bone osteonecrosis and offsets age-induced periodontal decay.

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Periapical bone response to bacterial lipopolysaccharide is shifted upon cyclooxygenase blockage

Cited by 16 publications

References 31 publications

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

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

Specialized pro-resolving lipid mediators in endodontics: a narrative review

Deficiency of the SMOC2 matricellular protein impairs bone healing and produces age-dependent bone loss

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