The effects of NLRP3 inflammasome inhibition or knockout in experimental apical periodontitis induced in mice.

OBJECTIVE: To evaluate the effects of NLRP3 inflammasome inhibition or knockout in experimental apical periodontitis (AP) induced in mice. METHODS: The experimental AP was induced by pulpal exposure. To evaluate NLRP3-specific inhibitor medication (MCC950), WT mice received intraperitoneal injections, while the control received PBS (n = 10). In addition, to evaluate NLRP3 knockout, 35 wild-type (WT) and 35 NLRP3-/- mice were divided into a control group (without pulpal exposure, n = 5) and three experimental groups: after 2, 14 and 42 days after pulpal exposure (n = 10). Microscopic and molecular analyzes were carried out using a significance level of 5%. RESULTS: Exposure to MCC950 did not affect the periapical lesion size after 14 days (P = 0.584). However, exposed mice had a lower expression of IL-1ß, IL-18 and caspase-1 (P = 0.010, 0.016 and 0.002, respectively). Moreover, NLRP3-/- mice showed a smaller periapical lesion after 14 and 42 days (P = 0.023 and 0.031, respectively), as well as a lower expression of IL-1ß after 42 days (P < 0.001), of IL-18 and caspase-1 after 14 (P < 0.001 and 0.035, respectively) and 42 days (P = 0.002 and 0.002, respectively). NLRP3-/- mice also showed a lower mRNA for Il-1ß, Il-18 and Casp1 after 2 (P = 0.002, 0.036 and 0.001, respectively) and 14 days (P = 0.002, 0.002 and 0.001, respectively). CONCLUSIONS: NLRP3 inflammasome inhibition or knockout can attenuate the inflammatory events that result in the periapical lesion (AP) formation after pulpal exposure in mice. CLINICAL RELEVANCE: The NLRP3 inflammasome may be a therapeutic target for AP, and new approaches may verify the impact of its inhibition (through intracanal medications or filling materials) on the bone repair process and treatment success.

The "oral" history of COVID-19: Primary infection, salivary transmission, and post-acute implications.

Severe acute respiratorysyndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has led to more than 3.25 million recorded deaths worldwide as of May 2021. COVID-19 is known to be clinically heterogeneous, and whether the reported oral signs and symptoms in COVID-19 are related to the direct infection of oral tissues has remained unknown. Here, we review and summarize the evidence for the primary infection of the glands, oral mucosae, and saliva by SARS-CoV-2. Not only were the entry factors for SARS-CoV-2 found in all oral tissues, but these were also sites of SARS-CoV-2 infection and replication. Furthermore, saliva from asymptomatic individuals contained free virus and SARS-CoV-2-infected oral epithelial cells, both of which were found to transmit the virus. Collectively, these studies support an active role of the oral cavity in the spread and transmission of SARS-CoV-2 infection. In addition to maintaining the appropriate use of personal protective equipment and regimens to limit microbial spread via aerosol or droplet generation, the dental community will also be involved in co-managing COVID-19 "long haulers"-now termed Post-Acute COVID-19 Syndrome. Consequently, we propose that, as SARS-CoV-2 continues to spread and as new clinical challenges related to COVID-19 are documented, oral symptoms should be included in diagnostic and prognostic classifications as well as plans for multidisciplinary care.

Porphyromonas gingivalis oral infection exacerbates the development and severity of collagen-induced arthritis.

INTRODUCTION: Clinical studies suggest a direct influence of periodontal disease (PD) on serum inflammatory markers and disease assessment of patients with established rheumatoid arthritis (RA). However, the influence of PD on arthritis development remains unclear. This investigation was undertaken to determine the contribution of chronic PD to immune activation and development of joint inflammation using the collagen-induced arthritis (CIA) model. METHODS: DBA1/J mice orally infected with Porphyromonas gingivalis were administered with collagen II (CII) emulsified in complete Freund's adjuvant (CFA) or incomplete Freund's adjuvant (IFA) to induce arthritis. Arthritis development was assessed by visual scoring of paw swelling, caliper measurement of the paws, mRNA expression, paw micro-computed tomography (micro-CT) analysis, histology, and tartrate resistant acid phosphatase for osteoclast detection (TRAP)-positive immunohistochemistry. Serum and reactivated splenocytes were evaluated for cytokine expression. RESULTS: Mice induced for PD and/or arthritis developed periodontal disease, shown by decreased alveolar bone and alteration of mRNA expression in gingival tissues and submandibular lymph nodes compared to vehicle. P. gingivalis oral infection increased paw swelling and osteoclast numbers in mice immunized with CFA/CII. Arthritis incidence and severity were increased by P. gingivalis in mice that received IFA/CII immunizations. Increased synovitis, bone erosions, and osteoclast numbers in the paws were observed following IFA/CII immunizations in mice infected with P gingivalis. Furthermore, cytokine analysis showed a trend toward increased serum Th17/Th1 ratios when P. gingivalis infection was present in mice receiving either CFA/CII or IFA/CII immunizations. Significant cytokine increases induced by P. gingivalis oral infection were mostly associated to Th17-related cytokines of reactivated splenic cells, including IL-1ß, IL-6, and IL-22 in the CFA/CII group and IL-1ß, tumor necrosis factor-α, transforming growth factor-ß, IL-6 and IL-23 in the IFA/CII group. CONCLUSIONS: Chronic P. gingivalis oral infection prior to arthritis induction increases the immune system activation favoring Th17 cell responses, and ultimately accelerating arthritis development. These results suggest that chronic oral infection may influence RA development mainly through activation of Th17-related pathways.

Implications of cultured periodontal ligament cells for the clinical and experimental setting: a review.

The periodontal ligament (PDL) is a key contributor to the process of regeneration of the periodontium. The heterogeneous nature of the PDL tissue, its development during early adulthood, and the different conditions to which the PDL tissue is exposed to in vivo impart on the PDL unique characteristics that may be of consequence during its cultivation in vitro. Several factors affecting the in vivo setting influence the behaviour of PDL fibroblasts in culture. The purpose of this review is to address distinct factors that influence the behaviour of PDL fibroblasts in culture -in vivo-in vitro transitions, cell identification/isolation markers, primary PDL cultures and cell lines, tooth-specific factors, and donor-specific factors. Based on the reviewed studies, the authors recommendations include the use of several identification markers to confirm cell identity, use of primary cultures at early passage to maintain unique PDL heterogeneic characteristics, and noting donor conditions such as age, systemic health status, and tooth health status. Continued efforts will expand our understanding of the in vitro and in vivo behaviour of cells, with the goal of orchestrating optimal periodontal regeneration. This understanding will lead to improved evidence-based rationales for more individualized and predictable periodontal regenerative therapies.

Effect of in vitro gingival fibroblast seeding on the in vivo incorporation of acellular dermal matrix allografts in dogs.

BACKGROUND: Acellular dermal matrix allograft (ADMA) has been used in various periodontal procedures with successful results. Because ADMA has no blood vessels or cells, slower healing and incorporation are observed compared to a subepithelial connective tissue graft. Fibroblasts accelerate the healing process by regulation of matrix deposition and synthesis of a variety of growth factors. Thus, the objective of this study was to evaluate histologically if gingival fibroblasts affect healing and incorporation of ADMA in dogs when used as a subepithelial allograft. METHODS: Gingival fibroblasts were established from explant culture from the connective tissue of keratinized gingiva collected from the maxilla of seven mongrel dogs. ADMA was seeded with gingival fibroblasts and transferred to dogs. Surgery was performed bilaterally, and the regions were divided into two groups: ADMA+F (ADMA containing fibroblasts) and ADMA (ADMA only). Biopsies were performed after 2, 4, and 8 weeks of healing. RESULTS: The quantity of blood vessels was significantly higher in the ADMA+F group at 2 weeks of healing (Kruskal-Wallis; P <0.05). There was no statistical difference (P >0.05) in the number of cell layers, epithelial area, or inflammatory infiltrate between the two groups at any stage of healing. CONCLUSION: The enhanced vascularization in vivo in early stages supports the important role of fibroblasts in improving graft performance and wound healing of cultured graft substitutes.

Uso de laser e placa oclusal na sensibilidade dentinária de bruxômanos / Use of laser and oclusal splint for dentin hypersensitivity of bruxers

A hipersensibilidade dentinária encontra-se presente numa grande parcela da população e indivíduos que apresentam parafunção oc1usal desenvolvem com mais freqüência, lesões cervicais não cariosas. Com o objetivo de avaliar o efeito da laserterapia de baixa intensidade sobre esse tipo de sensibilidade, formou-se um grupo com aplicações efetivas de laser e, um outro grupo com aplicações de laser e placa interoclusal. Em ambos os grupos, a sensibilidade dentinária foi mensurada utilizando-se uma escala visual analógica, antes e depois de cada uma das quatro aplicações de laser para análise do efeito imediato e também, 1 semana, 1 mês e 2 meses da última aplicação, para análise do efeito tardio. Os estímulos utilizados foram o contato de uma sonda exploradora na região cervical dos dentes e a aplicação de rápido jato de ar, via seringa tríplice. Os resultados mostraram que nos grupos 1 e 2 a sensibilidade dentinária foi maior frente ao estímulo jato de ar. A laserterapia apresentou efeitos benéficos, a cada aplicação, no grupo irradiado e, ao final de dois meses, manteve a melhoria frente ao estímulo jato de ar. No grupo 2, os resultados foram estatisticamente significantes nas quatro aplicações frente a ambos os estímulos e se mantiveram até o período final de observação.

Regeneration of class II furcation defects: determinants of increased success

As lesões de bifurcação classe II constituem uma das principais indicações para a técnica de regeneração tecidual guiada. Entretanto, a regeneração periodontal deste tipo de defeito ósseo, embora possível, não é considerada um resultado totalmente previsível, principalmente em termos de completo preenchimento ósseo. Muitos fatores podem explicar a variabilidade nos resultados do tratamento regenerativo nas lesões de bifurcação classe II. O objetivo desta revisão de literatura foi avaliar o significado de fatores relacionados ao paciente (fumo, estresse, diabetes mellitus, AIDS e outras doenças agudas e debilitantes, e presença de bolsas periodontais em outros sítios da boca), às condições locais (anatomia da furca, morfologia do defeito, espessura gengival e mobilidade dentária), ao tratamento cirúrgico (controle de infecção, utilização de materiais para preenchimento ósseo, tipo de membrana e técnica cirúrgica) e ao período pós-operatório (controle de placa, exposição e remoção das membranas e terapia periodontal de suporte) para o sucesso da RTG no tratamento das lesões de bifurcação classe II.

Regeneration of class II furcation defects: determinants of increased success.

One of the most important indications for guided tissue regeneration (GTR) treatment is class II furcation lesion. However, periodontal regeneration of this type of defect, although possible, is not considered totally predictable, especially in terms of complete bone fill. Many factors may account for variability in the response to regenerative therapy in class II furcation. The purpose of this review is to assess the prognostic significance of factors related to the patient (smoking, stress, diabetes mellitus, acquired immunodeficiency syndrome and other acute and debilitating diseases, and the presence of multiple deep periodontal pockets), local factors (furcal anatomy, defect morphology, thickness of gingival tissue and tooth mobility), surgical treatment (infection control, bone replacement grafts combined with barriers or GTR alone, type of barrier and surgical technique), and postoperative period (plaque control, membrane exposure, membrane retrieval and a regular supportive periodontal care program) for successful of GTR in class II furcations.