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Pathologic tooth migration related to periodontal disease is a common chief complaint of periodontal patients. This paper describes the treatment of a case of severe periodontal disease and disfiguring pathologic migration of maxillary central incisors, which required a multidisciplinary approach. After conventional periodontal treatment was performed, the anterior diastema was closed using a combination of orthodontic therapy and restorative treatment. A 6-month follow-up examination of this case revealed resolution of the anterior pathologic migration, with gains in clinical attachment levels and a successful esthetic and functional final result. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Inflammatory diseases often coincide with reduced bone mass. Mechanoresponsive osteocytes regulate bone mass by maintaining the balance between bone formation and resorption. Despite its biologic significance, the effect of inflammation on osteocyte mechanoresponsiveness is not understood. To fill this gap, we investigated whether the inflammatory cytokines tumor necrosis factor alpha (TNFalpha) and interleukin-1beta (IL-1beta) modulate the osteocyte response to mechanical loading. METHODS: MLO-Y4 osteocytes were incubated with TNFalpha (0.5-30 ng/ml) or IL-1beta (0.1-10 ng/ml) for 30 minutes or 24 hours, or with calcium inhibitors for 30 minutes. Cells were subjected to mechanical loading by pulsatile fluid flow (mean +/- amplitude 0.7 +/- 0.3 Pa, 5 Hz), and the response was quantified by measuring nitric oxide (NO) production using Griess reagent and by measuring intracellular calcium concentration ([Ca(2+)](i)) using Fluo-4/AM. Focal adhesions and filamentous actin (F-actin) were visualized by immunostaining, and apoptosis was quantified by measuring caspase 3/7 activity. Cell-generated tractions were quantified using traction force microscopy, and cytoskeletal stiffness was quantified using optical magnetic twisting cytometry. RESULTS: Pulsatile fluid flow increased [Ca(2+)](i) within seconds (in 13% of cells) and NO production within 5 minutes (4.7-fold). TNFalpha and IL-1beta inhibited these responses. Calcium inhibitors decreased pulsatile fluid flow-induced NO production. TNFalpha and IL-1beta affected cytoskeletal stiffness, likely because 24 hours of incubation with TNFalpha and IL-1beta decreased the amount of F-actin. Incubation with IL-1beta for 24 hours stimulated osteocyte apoptosis. CONCLUSION: Our results suggest that TNFalpha and IL-1beta inhibit mechanical loading-induced NO production by osteocytes via abrogation of pulsatile fluid flow-stimulated [Ca(2+)](i), and that IL-1beta stimulates osteocyte apoptosis. Since both NO and osteocyte apoptosis affect osteoclasts, these findings provide a mechanism by which inflammatory cytokines might contribute to bone loss and consequently affect bone mass in rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

AIM: To assess orthodontic intrusion effects on periodontal tissues in dogs' pre-molars with class III furcations treated with open flap debridement (OFD) or with guided tissue regeneration (GTR) associated to bone autograft (BA). MATERIAL AND METHODS: Class III furcations were created in the pre-molars of seven mongrel dogs. After 75 days, teeth were randomly treated with OFD or GTR/BA. After 1 month, metallic crowns were assembled on pre-molars and connected apically to mini-implants by nickel-titanium springs. Teeth were randomly assigned to orthodontic intrusion (OFD+I and GTR/BA+I) groups or no movement (OFD and GTR/BA) groups. Dogs were sacrificed after 3 months of movement and 1 month retention. RESULTS: All class III furcations were closed or reduced to class II or I in the intrusion groups, while 50% of the lesions in non-moved teeth remained unchanged. Intruded teeth presented higher probing depth and lower gingival marginal level than non-moved teeth (p<0.01). Clinical attachment gain was reduced in the intrusion groups by the end of retention (p<0.05). OFD+I presented smaller soft tissue area and larger bone tissue area than other groups (p<0.05). CONCLUSION: Orthodontic intrusion with anchorage via mini-implants improved the healing of class III furcation defects after OFD in dogs. GTR/BA impaired those results. [ABSTRACT FROM AUTHOR]

PURPOSE: The effect of orthodontic movement on the periodontal tissues of maxillary second pre-molars, after regenerative treatment for class II furcations, was evaluated in four mongrel dogs. MATERIAL AND METHODS: Class II furcation lesions were created. After 75 days they were treated with bovine bone mineral matrix and guided tissue regeneration with absorbable membrane. After 2 months of daily plaque control, each of the dog's furcation pre-molars was randomly assigned to a test or control group. Orthodontic appliances were placed on both sides of the maxilla using third pre-molars and canines as anchorages. In the test group, bodily orthodontic movement of the second pre-molars was performed in the mesial direction for 3 months while control pre-molars remained unmoved. The dogs were sacrificed for histometric and histologic analyses. RESULTS: There were no statistically significant differences between the two groups in total bone and biomaterial areas or linear extension of periodontal regeneration on the radicular surfaces. In the test group, however, there was a tendency to a greater quantity of bone and a lesser quantity of biomaterial. CONCLUSION: The orthodontic movement was not pre-judicial to the results obtained with the regenerative periodontal treatment. [ABSTRACT FROM AUTHOR]

Purpose: Autophagy is an important adaptive process for mechanotransduction, in which Damage-Regulated Autophagy Modulator 1 (DRAM1) has a key function in cell fate determination. This study aimed to analyze the influence of biomechanical loading on DRAM1 expression in periodontal cells and tissues., Methods: Human periodontal ligament (PDL) fibroblasts were stimulated with different pressure protocols, physiological load and overload, in the presence and absence of autophagy inhibitor 3-methyladenine (3-MA) and compared with untreated cells. DRAM1 expression was measured using real-time PCR and ELISA after 1 d and 2 d. DRAM1 expression was determined in gingival biopsies of rats, and gene expression of DRAM1 was analyzed after 1 d, 7 d, and 15 d of orthodontic treatment. Statistical analysis was carried out using ANOVA and post-hoc tests., Results: Overload led to increased DRAM1 gene expression after 1 d, while physiological load did not change DRAM1 expression. After 2 d, DRAM1 expression was increased in both groups. Protein levels were elevated after 2 d of pressure application of both magnitudes, while no significant increase was evident after 1 d. Treatment with 3-MA led to a significant reduction in DRAM1 gene expression in both pressure groups, while it remained unchanged in the control group. In vivo, DRAM1 was located in the periodontal ligament, and we could determine an orthodontic force-mediated increase in DRAM1 gene expression at 7 d and 15 d., Conclusion: This study indicates a dependence of DRAM1 regulation on the duration and magnitude of bio-mechanical loading and on autophagy-associated pathways., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Svenja Beisel-Memmert reports financial support was provided by Deutsche Forschungsgemeinschaft (DFG, German Research Foundation). Christian Behl reports financial support was provided by Corona-Stiftung im Stiftverband für die Deutsche Wissenschaft. Andreas Jaeger reports financial support was provided by Medical Faculty of the University of Bonn. Christian Kirschneck reports financial support was provided by Medical Faculty of the University of Bonn. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Periodontal disease affects over 1 billion people globally. This study investigated how periodontitis affects the protein profile of the periodontal ligament (PDL) in rats. Eight Holtzman rats were divided into control and experimental periodontitis groups. The PDL was isolated using laser capture microdissection and protein extracts were analyzed by mass spectrometry. Data analysis utilized specialized software, and Gene Ontology enrichment analysis identified significant protein functions. The data are available via ProteomeXchange with identifier PXD055817. Proteins such as SerpinB1, C5, and Lgals3 were validated through immunohistochemistry, and their gene expression was examined in an in vitro human PDL cell line. This study identified 1326 proteins, with 156 unique to the control group, 294 unique to the periodontitis group, and 876 common to both groups. Enrichment analysis revealed that proteins associated with the regulation of enzyme activity and RNA binding were significantly represented in the periodontitis group. There were increased levels of SerpinB1, C5, and Lgals3 in the periodontitis group based on proteomic and immunohistochemical analyses. Furthermore, these targets showed increased gene expression in stimulated human PDL cells. This study provides insights into the periodontitis-related alterations in the protein composition of the PDL and PDL cells, identifying both novel and previously known disease-associated proteins. SIGNIFICANCE: The periodontal ligament plays a crucial role in oral functions by providing structural support to the tooth. Due to the presence of undifferentiated mesenchymal cells, research into its regenerative capacity is ongoing. Pathological conditions can affect these functions and protein composition. Currently, there is a lack of comprehensive research specifically focusing on evaluating the periodontal ligament in both healthy and diseased states. This pioneering study screened for protein alterations and the mechanisms related to periodontitis. The possibility of using proteomic analysis to evaluate the protein alterations that occur in periodontitis, a disease with a high global incidence, could provide therapeutic targets and new biomarkers for future clinical studies., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2025. Published by Elsevier B.V.)

Objectives: This study aimed to investigate the osseointegration of titanium (Ti) implants with micro-nano textured surfaces functionalized with strontium additions (Sr) in a pre-clinical rat tibia model., Methodology: Ti commercially pure (cp-Ti) implants were installed bilaterally in the tibia of 64 Holtzman rats, divided into four experimental groups (n=16/group): (1) Machined surface - control (C); (2) Micro-nano textured surface treatment (MN); (3) Micro-nano textured surface with Sr2+ addition (MNSr); and (4) Micro-nano textured surface with a higher complementary addition of Sr2+ (MNSr+). In total, two experimental euthanasia periods were assessed at 15 and 45 days (n=8/period). The tibia was subjected to micro-computed tomography (μ-CT), histomorphometry with the EXAKT system, removal torque (TR) testing, and gene expression analysis by PCR-Array of 84 osteogenic markers. Gene expression and protein production of bone markers were performed in an in vitro model with MC3T3-E1 cells. The surface characteristics of the implants were evaluated by scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), and laser scanning confocal microscopy., Results: SEM, confocal, and EDS analyses demonstrated the formation of uniform micro-nano textured surfaces in the MN group and Sr addition in the MNSr and MNSr+ groups. TR test indicated greater osseointegration in the 45-day period for treated surfaces. Histological analysis highlighted the benefits of the treatments, especially in cortical bone, in which an increase in bone-implant contact was found in groups MN (15 days) and MNSr (45 days) compared to the control group. Gene expression analysis of osteogenic activity markers showed modulation of various osteogenesis-related genes. According to the in vitro model, RT-qPCR and ELISA demonstrated that the treatments favored gene expression and production of osteoblastic differentiation markers., Conclusions: Micro-nano textured surface and Sr addition can effectively improve and accelerate implant osseointegration and is, therefore, an attractive approach to modifying titanium implant surfaces with significant potential in clinical practice.

Objective: This study assessed the impact of an anti-sclerostin monoclonal antibody (Scl-Ab)-based osteoporosis drug on the post-extraction alveolar repair of ovariectomized rats., Design: Fifteen female rats were randomly distributed into three groups: CTR (healthy animals), OST (osteoporosis induced by ovariectomy), and OST+Scl-Ab (osteoporosis induction followed by Scl-Ab treatment). Ovariectomy or sham surgery was performed 30 days before baseline, and Scl-Ab or a vehicle was administered accordingly in the groups. After seven days, all rats underwent the first lower molar extraction and were euthanized 15 days later. Computed microtomography, histological analysis, and collagen content measurement were performed on post-extraction sockets and intact mandibular and maxillary bone areas., Results: Microtomographic analyses of the sockets and mandibles did not reveal significant differences between groups on bone morphometric parameters (p > 0.05), while maxillary bone analyses resulted in better maintenance of bone architecture in OST+Scl-Ab, compared to OST (p < 0.05). Descriptive histological analysis and polarization microscopy indicated better post-extraction socket repair characteristics and collagen content in OST+Scl-Ab compared to OST (p < 0.05)., Conclusions: Scl-Ab-based medication did not accelerate alveolar bone formation but exhibited better post-extraction repair characteristics, and collagen content compared to ovariectomized animals only., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Gabriel Henrique Perles reports financial support was provided by São Paulo State University. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study aimed to evaluate the osteogenic potential of hydroxyapatite (HA), Alginate (Alg), and Gelatine (Gel) composite in a critical-size defect model in rats. Twenty-four male rats were divided into three groups: a negative control with no treatment (Control group), a positive control treated with deproteinized bovine bone mineral (DBBM group), and the experimental group treated with the new HA-Alg-Gel composite (HA-Alg-Gel group). A critical size defect (8.5mm) was made in the rat's calvaria, and the bone formation was evaluated by in vivo microcomputed tomography analysis (µCT) after 1, 15, 45, and 90 days. After 90 days, the animals were euthanized and histological and histomorphometric analyses were performed. A higher proportion of mineralized tissue/biomaterial was observed in the DBBM group when compared to the HA-Alg-Gel and Control groups in the µCT analysis during all analysis periods. However, no differences were observed in the mineralized tissue/biomaterial proportion observed on day 1 (immediate postoperative) in comparison to later periods of analysis in all groups. In the histomorphometric analysis, the HA-Alg-Gel and Control groups showed higher bone formation than the DBBM group. Moreover, in histological analysis, five samples of the HA-Alg-Gal group exhibited formed bone spicules adjacent to the graft granules against only two of eight samples in the DBBM group. Both graft materials ensured the maintenance of defect bone thickness, while a tissue thickness reduction was observed in the control group. In conclusion, this study demonstrated the osteoconductive potential of HA-Alg-Gel bone graft by supporting new bone formation around its particles.

This systematic review aims to identify and discuss the most used methodologies in pre-clinical studies for the evaluation of the implementation of dental implants in systemically compromised pigs and sheep. This study provides support and guidance for future research, as well as for the prevention of unnecessary animal wastage and sacrifice. Preferred Reporting for Systematic Reviews and Meta-Analyses (PRISMA) was used as a guideline; electronic searches were performed in PubMed, Scopus, Scielo, Web of Science, Embase, Science Direct, Brazilian Bibliography of Dentistry, Latin American and Caribbean Literature in Health Sciences, Directory of Open Access Journals, Database of Abstracts of Reviews of Effects, and gray literature until January 2022 (PROSPERO/CRD42021270119). Sixty-eight articles were chosen from the 2439 results. Most studies were conducted in pigs, mainly the Göttinger and Domesticus breeds. Healthy animals with implants installed in the jaws were predominant among the pig studies. Of the studies evaluating the effect of systemic diseases on osseointegration, 42% were performed in osteoporotic sheep, 32% in diabetic sheep, and 26% in diabetic pigs. Osteoporosis was primarily induced by bilateral ovariectomy and mainly assessed by X-ray densitometry. Diabetes was induced predominantly by intravenous streptozotocin and was confirmed by blood glucose analysis. Histological and histomorphometric analyses were the most frequently employed in the evaluation of osseointegration. The animal models presented unique methodologies for each species in the studies that evaluated dental implants in the context of systemic diseases. Understanding the most commonly used techniques will help methodological choices and the performance of future studies in implantology.

Cysteine proteases orchestrate bone remodeling, and are inhibited by cystatins. In reinforcing our hypothesis that exogenous and naturally obtained inhibitors of cysteine proteases (cystatins) act on bone remodeling, we decided to challenge osteoblasts with sugarcane-derived cystatin (CaneCPI-5) for up to 7 days. To this end, we investigated molecular issues related to the decisive, preliminary stages of osteoblast biology, such as adhesion, migration, proliferation, and differentiation. Our data showed that CaneCPI-5 negatively modulates both cofilin phosphorylation at Ser03, and the increase in cytoskeleton remodeling during the adhesion mechanism, possibly as a prerequisite to controlling cell proliferation and migration. This is mainly because CaneCPI-5 also caused the overexpression of the CDK2 gene, and greater migration of osteoblasts. Extracellular matrix remodeling was also evaluated in this study by investigating matrix metalloproteinase (MMP) activities. Our data showed that CaneCPI-5 overstimulates both MMP-2 and MMP-9 activities, and suggested that this cellular event could be related to osteoblast differentiation. Additionally, differentiation mechanisms were better evaluated by investigating Osterix and alkaline phosphatase (ALP) genes, and bone morphogenetic protein (BMP) signaling members. Altogether, our data showed that CaneCPI-5 can trigger biological mechanisms related to osteoblast differentiation, and broaden the perspectives for better exploring biotechnological approaches for bone disorders., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could influence the research reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The peroxisome proliferator-activated receptor gamma ( PPARG ) gene encodes a transcription factor involved in the regulation of complex metabolic and inflammatory diseases. We investigated whether single nucleotide polymorphisms (SNPs) and haplotypes of the PPARG gene could contribute with susceptibility to develop periodontitis alone or together with type 2 diabetes mellitus (T2DM). Moreover, we evaluated the gene-phenotype association by assessing the subjects' biochemical and periodontal parameters, and the expression of PPARG and other immune response-related genes. We examined 345 subjects with a healthy periodontium and without T2DM, 349 subjects with moderate or severe periodontitis but without T2DM, and 202 subjects with moderate or severe periodontitis and T2DM. PPARG SNPs rs12495364, rs1801282, rs1373640, and rs1151999 were investigated. Multiple logistic regressions adjusted for age, sex, and smoking status showed that individuals carrying rs1151999-GG had a 64% lower chance of developing periodontitis together with T2DM. The CCGT haplotype increased the risk of developing periodontitis together with T2DM. The rs1151999-GG and rs12495364-TC were associated with reduced risk of obesity, periodontitis, elevated triglycerides, and elevated glycated hemoglobin, but there was no association with gene expression. Polymorphisms of the PPARG gene were associated with developing periodontitis together with T2DM, and with obesity, lipid, glycemic, and periodontal characteristics.

This study aimed to assess the obesity effects on the proteomic profile of the periodontal ligament of rats submitted to obesity induction by a high-fat diet. Eight Holtzman rats were divided into control (n = 3) and obese (n = 5) groups. The maxillae were histologically processed for laser capture microdissection of the periodontal ligament of the first maxillary molars. Peptide mixtures were analyzed by LC-MS/MS. A total of 1379 proteins were identified in all groups. Among them, 335 (24.30%) were exclusively detected in the obese group, while 129 (9.35%) proteins were uniquely found in the control group. Out of the 110 (7.98%) differentially abundant proteins, 10 were more abundant and 100 had decreased abundance in the obese group. A gene ontology analysis showed some proteins related to obesity in the “extracellular exosome” term among differentially identified proteins in the gene ontology cellular component terms Prelp, Sec13, and Sod2. These three proteins were upregulated in the obese group (p < 0.05), as shown by proteomic and immunohistochemistry analyses. In summary, our study presents novel evidence that the proteomic profile of the periodontal ligament is altered in experimental obesity induction, providing a list of differentially abundant proteins associated with obesity, which indicates that the periodontal ligament is responsive to obesity.

This study aims to evaluate the potential of a novel biomaterial synthesized from amorphous calcium phosphate (ACP), octacalcium phosphate (OCP), and hydroxyapatite (HA) to repair critical-sized defects (CSD) in rabbit calvaria. In vitro analyses of cell viability, cell proliferation, formation of mineral nodules, and cell differentiation using qPCR were performed for comparing experimental calcium phosphate (ECP), deproteinized bovine bone (DBB), and beta-tricalcium phosphate (β-TCP). Bilateral CSDs were created in 45 rabbit calvaria. Six groups were evaluated: ECP, ECP + fibrin sealant (ECP + S), coagulum, autogenous bone, DBB, and β-TCP. Euthanasia was performed at 2, 4, and 8 weeks, followed by micro-computed tomography and histological and immunohistochemical analyses. Results from in vitro analyses revealed similar biocompatibility for all tested materials and a tendency for higher gene expression of some bone markers in the ECP group than in β-TCP and DBB groups at 7 days. In contrast to that in DBB and β-TCP groups, ECP displayed growing bone volume over total volume percentage (BV/TV%) with time in vivo. Histological analysis revealed a greater number of giant cells and reduced size of grafted particles in ECP during all periods of analysis. RUNX-2 expression was statistically lower in ECP than DBB at 2 and 4 weeks. Despite no statistical significance, ECP presented the highest absolute values for ALP-expression at 2, 4, and 8 weeks compared with other groups. Together, our findings indicate that a combination of the ACP, OCP, and HA phases into ECP is beneficial and promising for bone regeneration., (© 2022 Wiley Periodicals LLC.)

Objectives: This study aimed to investigate polymorphisms in genes considered molecular biomarkers of type 2 diabetes mellitus (T2DM) to assess whether they are associated with periodontitis, and relating them to the periodontal status, glycemic and lipid profile of the subjects., Design: We investigated individuals who underwent complete periodontal examination and biochemical evaluation. We categorized them into three groups: (i) periodontitis with T2DM (Periodontitis+T2DM group, n = 206); (ii) periodontitis without T2DM (Periodontitis group, n = 346); and (iii) healthy individuals without Periodontitis or T2DM (Healthy group, n = 345). We investigated three single nucleotide polymorphisms (SNPs) for AGER, RBMS1 and VEGFA genes. We applied multivariate logistic and multiple linear regression models for all groups and stratified the subjects by sex and smoking habits., Results: Compared with RBMS1-rs7593730-CC+CT genotype carriers, RBMS1-rs7593730-TT carriers were more susceptible to periodontitis [odds ratio (OR) = 2.29; 95% confidence interval (CI) = 1.04-5.01; P-value = 0.033]. Among AGER-rs184003-CC carriers, never smokers had reduced risks of periodontitis and Periodontitis+T2DM than ever smokers. For either RBMS1-rs7593730-CC or VEGFA-rs9472138-CC carriers, never smokers had less susceptibility to develop periodontitis than ever smokers. Compared with AGER-rs184003-CC carriers, AGER-rs184003-AA carriers presented fewer remaining teeth. VEGFA-rs9472138-TT carriers showed a lower percentage of sites with characteristics of active periodontal disease (bleeding on pocket probing and interproximal clinical attachment level) compared with VEGFA-rs9472138-CC carriers., Conclusions: In the studied population, AGER rs184003, RBMS1 rs7593730, and VEGFA rs9472138, which are considered genetic markers for T2DM, were associated with periodontitis without T2DM or periodontitis together with T2DM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The prevalence of obesity has increased significantly worldwide. Therefore, this study aimed to evaluate the influence of obesity on the proteomic profile of periodontal ligament (PDL) tissues of rat first maxillary molars (1 M) submitted to orthodontic tooth movement (OTM). Ten Holtzman rats were distributed into two groups (n = 5): the M group (OTM), and the OM group (obesity induction plus OTM). Obesity was induced by a high-fat diet for the entire experimental periods After that period, the animals were euthanized and the hemimaxillae removed and processed for laser capture microdissection of the PDL tissues of the 1 M. Peptide extracts were obtained and analyzed by LC-MS/MS. Data are available via ProteomeXchange with identifier PXD033647. Out of the 109 proteins with differential abundance, 49 were identified in the OM group, including Vinculin, Cathepsin D, and Osteopontin, which were selected for in situ localization by immunohistochemistry analysis (IHC). Overall, Gene Ontology (GO) analysis indicated that enriched proteins were related to the GO component cellular category. IHC validated the trends for selected proteins. Our study highlights the differences in the PDL proteome profiling of healthy and obese subjects undergoing OTM. These findings may provide valuable information needed to better understand the mechanisms involved in tissue remodeling in obese patients submitted to orthodontic treatment. SIGNIFICANCE: The prevalence of obesity is increasing worldwide. Emerging findings in the field of dentistry suggest that obesity influences the tissues around the teeth, especially those in the periodontal ligament. Therefore, evaluation of the effect of obesity on periodontal tissues remodeling during orthodontic tooth movement is a relevant research topic. To our knowledge, this is the first study to evaluate proteomic changes in periodontal ligament tissue in response to the association between orthodontic tooth movement and obesity. Our study identified a novel protein profile associated with obesity by using laser microdissection and proteomic analysis, providing new information to increase understanding of the mechanisms involved in obese patients undergoing orthodontic treatment which can lead to a more personalized orthodontic treatment approach., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Hereditary hemorrhagic telangiectasia (HHT) is a rare condition in which fragile vascular walls lead to increased risks of bleeding, cerebral abscesses, arteriovenous malformations, anemia, and thrombosis. To date, no protocol has been established for optimizing the clinical outcomes of periodontal treatment in patients with this condition. The aim of this case report is to describe a safe clinical approach to periodontal treatment in a patient with HHT. A 39-year-old woman had a history of multiple macules on the oral mucosa, and a diagnosis of HHT was made based on the Curaçao diagnostic criteria (epistaxis, telangiectases, visceral lesions, and family history). Evaluation of the patient's periodontal clinical parameters and radiographs led to a diagnosis of generalized periodontitis, stage IV, grade C. The patient underwent nonsurgical periodontal therapy consisting of supragingival and subgingival scaling and root planing under a careful and specific protocol that included antibiotic prophylaxis before each session. Two months after therapy, the periodontal reevaluation showed improvement in the clinical parameters at most sites. Sites with remaining periodontal pockets were re-treated according to the same protocol, including the antibiotic prophylaxis. The patient was enrolled in a periodontal maintenance program, and her HHT was routinely monitored by her physician. Periodontal treatment may promote secondary complications in patients with HHT if appropriate systemic care is not provided, and the periodontal treatment plan should be designed individually for each patient. Establishing the correct HHT diagnosis and coordinating care with the patient's physician are essential to safe, effective treatment.

The titanium alloy composition and microdesign affect the dynamic interplay between the bone cells and titanium surface in the osseointegration process. The current study aimed to evaluate the surface physicochemical properties, electrochemical stability, and the metabolic response of the MC3T3-E1 cells (pre-osteoblast cell line) cultured onto titanium-15molybdenum (Ti-15Mo) discs treated with phosphoric acid (H 3 PO 4 ) and sodium hydroxide (NaOH) and/or strontium-loading by the hydrothermal method. The x-ray dispersive energy spectroscopy (EDS) and x-ray diffraction (XRD) analysis showed no trace of impurities and the possible formation of hydrated strontium oxide (H 2 O 2 Sr), respectively. The confocal laser microscopy (CLSM) analysis indicated that titanium samples treated with strontium (Sr) showed greater surface roughness. The acid/alkali treatment prior to the hydrothermal Sr deposition improved the surface free energy and resistance to corrosion of the Ti-15Mo alloy. The acid/alkali treatment also provided greater retention of the Sr particles on the Ti-15Mo surfaces accordingly with inductively coupled plasma optical emission spectrometry (ICP-OES) analysis. The AlamarBlue and fluorescence analysis indicated noncytotoxic effects against the MC3T3-E1 cells, which allowed cells' adhesion and proliferation, with greater cells' spreading in the Sr-loaded Ti-15Mo samples. These findings suggest that Sr deposition by the hydrothermal method has the potential to enhance the physicochemical properties of the Ti-15Mo previously etched with H 3 PO 4 and NaOH, and also improve the initial events related to cell-mediated bone deposition., (© 2022 IOP Publishing Ltd.)

Background and Objectives: Many studies have been conducted to better understand the molecular mechanism involved with periodontitis progression. There has been growing interest in the potential impact of obesity on periodontitis onset and progression, but the mechanisms involved remain to be elucidated. The present study was designed to determine the impact of obesity on experimentally induced periodontitis in rats and identify novel pathways involved., Methods: Sixteen Holtzman rats were distributed into two groups (n = 8): ligature-induced periodontitis (P) and obesity plus ligature-induced periodontitis (OP). Obesity was induced by a high-fat diet for 70 days, whereas periodontitis was induced for 20 days, with a cotton thread placed around the upper first molars bilaterally. Alveolar bone loss was measured by microtomographic analysis and histologically by histometry on the hemimaxillae. The protein composition of the periodontal ligament was evaluated by proteomic analysis., Results: Data analysis (body weight, adipose tissue weight, and blood test) confirmed obesity induction, whereas bone loss was confirmed by micro-CT and histologic analyses. Proteome analysis from the periodontal ligament tissues (PDL) identified 819 proteins, 53 exclusive to the P group, 28 exclusive to the OP group, and 738 commonly expressed. Validation was performed by immunohistochemistry for selected proteins (spondin1, vinculin, and TRAP)., Conclusion: Histologically, it was found that obesity did not significantly affect bone loss resulting from periodontitis. However, the present study's findings indicated that obesity affects the proteome of PDL submitted to experimental periodontitis, allowing for identifying potential targets for personalized approaches., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Periodontitis, a highly prevalent multicausal chronic inflammatory and destructive disease, develops as a result of complex host-parasite interactions. Dysbiotic bacterial biofilm in contact with the gingival tissues initiates a cascade of inflammatory events, mediated and modulated by the host's immune response, which is characterized by increased expression of several inflammatory mediators such as cytokines and chemokines in the connective tissue. If periodontal disease (PD) is left untreated, it results in the destruction of the supporting tissues around the teeth, including periodontal ligament, cementum, and alveolar bone, which lead to a wide range of disabilities and poor quality of life, thus imposing significant burdens. This process depends on the differentiation and activity of osteoclasts, the cells responsible for reabsorbing the bone tissue. Therefore, the inhibition of differentiation or activity of these cells is a promising strategy for controlling bone resorption. Several pharmacological drugs that target osteoclasts and inflammatory cells with immunomodulatory and anti-inflammatory effects, such as bisphosphonates, anti-RANK-L antibody, strontium ranelate, cathepsin inhibitors, curcumin, flavonoids, specialized proresolving mediators, and probiotics, were already described to manage inflammatory bone resorption during experimental PD progression in preclinical studies. Meantime, a growing number of studies have described the beneficial effects of herbal products in inhibiting bone resorption in experimental PD. Therefore, this review summarizes the role of several pharmacological drugs used for PD prevention and treatment and highlights the targeted action of all those drugs with antiresorptive properties. In addition, our review provides a timely and critical appraisal for the scientific rationale use of the antiresorptive and immunomodulatory medications in preclinical studies, which will help to understand the basis for its clinical application., Competing Interests: The authors declare no conflicts of interest to report regarding the present study., (Copyright © 2022 Angelica Leticia Reis Pavanelli et al.)

The effect of bacterial infection on the expression of growth hormone secretagogue receptor (GHS-R) was investigated in periodontal cells and tissues, and the actions of ghrelin were evaluated. GHS-R was assessed in periodontal tissues of rats with and without periodontitis. Human gingival fibroblasts (HGFs) were exposed to Fusobacterium nucleatum in the presence and absence of ghrelin. GHS-R expression was determined by real-time PCR and immunocytochemistry. Furthermore, wound healing, cell viability, proliferation, and migration were evaluated. GHS-R expression was significantly higher at periodontitis sites as compared to healthy sites in rat tissues. F. nucleatum significantly increased the GHS-R expression and protein level in HGFs. Moreover, ghrelin significantly abrogated the stimulatory effects of F. nucleatum on CCL2 and IL-6 expressions in HGFs and did not affect cell viability and proliferation significantly. Ghrelin stimulated while F. nucleatum decreased wound closure, probably due to reduced cell migration. Our results show original evidence that bacterial infection upregulates GHS-R in rat periodontal tissues and HGFs. Moreover, our study shows that ghrelin inhibited the proinflammatory actions of F. nucleatum on HGFs without interfering with cell viability and proliferation, suggesting that ghrelin and its receptor may act as a protective molecule during bacterial infection on periodontal cells.

The present case series aimed to evaluate the use of a Digital Smile Design (DSD) and mock-up technique for esthetic crown lengthening (ECL) surgery in six clinical cases with a 2-year follow-up. Six nonsmoker patients (five females, one male; aged 22 to 32 years), periodontally and systemically healthy, with inadequate tooth width/height ratio proportions associated with a gingival misalignment in the anterior maxilla were included. The DSDs were created using PowerPoint for all patients to evaluate gingival level and tooth form/contour. A wax-up and mock-up were created based on the DSD measurements. ECL surgeries were performed in all cases using the mock-up technique to determine the final gingival margin position and the amount of bone resection needed. A mock-up to bone crest distance of 3 mm was obtained in all cases. Using patient photographs, comparisons were made between the dental crown length (DCL) measurements obtained before the surgical procedure (baseline; T0), on the DSD template immediately postoperatively (IPO; T1), and at the 2-year follow-up (T2). A DCL augmentation of 1.16 ± 0.68 mm was obtained at T1, with an augmentation of 1.03 ± 0.73 mm at T2. Moreover, a minimal difference of 0.34 ± 0.74 mm between the DCL planned in the DSD template and the DCL obtained IPO was observed. In conclusion, the ECL procedure based on the DSD concept and mock-up technique proposed in this cases series was a predictable protocol for smile disharmony treatment in all the patients.

Periodontal disease (PD) is a polymicrobial chronic inflammatory condition of the supporting tissues around the teeth, leading to the destruction of surrounding connective tissue. During the progression of PD, osteoclasts play a crucial role in the resorption of alveolar bone that eventually leads to the loss of teeth if the PD is left untreated. Therefore, the development of antiresorptive therapies targeting bone-resorbing cells will significantly benefit the treatment of PD. Here, we demonstrate the inhibitory effect of CsinCPI-2, a novel cysteine peptidase inhibitor from the orange tree, on periodontitis-induced inflammation, alveolar bone loss, and osteoclast differentiation. Using the ligature-induced periodontitis model in mice, we show that treatment with CsinCPI-2 (0.8 µg/g of body weight) significantly reduced inflammatory cell infiltrate in the connective tissue and prevented the loss of alveolar bone mass (BV/TV) caused by PD, effects associated with diminished numbers of TRAP-positive multinucleated cells. Furthermore, CsinCPI-2 significantly downregulated the numbers of inflammatory cells expressing CD3, CD45, MAC387, and IL-1β. In vitro, CsinCPI-2 inhibited RANKL-induced TRAP+ multinucleated osteoclast formation in mouse bone marrow macrophage cultures in a concentration-dependent manner. This effect was not due to cytotoxicity, as demonstrated by the MTT assay. CsinCPI-2 inhibited RANKL-induced mRNA expression of Acp5 , Calcr , and Ctsk , as well as the RANKL-induced upregulation of Nfatc1, a crucial transcription factor for osteoclast differentiation. Based on our findings, CsinCPI-2 prevents bone loss induced by PD by controlling the inflammatory process and acting directly on osteoclastogenesis, suggesting an interesting potential for CsinCPI-2 in the strategy for PD treatment.

Objectives: The aim of this in vitro and in vivo study was to investigate the interaction of periodontitis and orthodontic tooth movement on interleukin (IL)-6 and C-X-C motif chemokine 2 (CXCL2)., Materials and Methods: The effect of periodontitis and/or orthodontic tooth movement (OTM) on alveolar bone and gingival IL-6 and CXCL2 expressions was studied in rats by histology and RT-PCR, respectively. The animals were assigned to four groups (control, periodontitis, OTM, and combination of periodontitis and OTM). The IL-6 and CXCL2 levels were also studied in human gingival biopsies from periodontally healthy and periodontitis subjects by RT-PCR and immunohistochemistry. Additionally, the synthesis of IL-6 and CXCL2 in response to the periodontopathogen Fusobacterium nucleatum and/or mechanical strain was studied in periodontal fibroblasts by RT-PCR and ELISA., Results: Periodontitis caused an increase in gingival levels of IL-6 and CXCL2 in the animal model. Moreover, orthodontic tooth movement further enhanced the bacteria-induced periodontal destruction and gingival IL-6 gene expression. Elevated IL-6 and CXCL2 gingival levels were also found in human periodontitis. Furthermore, mechanical strain increased the stimulatory effect of F. nucleatum on IL-6 protein in vitro., Conclusions: Our study suggests that orthodontic tooth movement can enhance bacteria-induced periodontal inflammation and thus destruction and that IL-6 may play a pivotal role in this process., Clinical Relevance: Orthodontic tooth movement should only be performed after periodontal therapy. In case of periodontitis relapse, orthodontic therapy should be suspended until the periodontal inflammation has been successfully treated and thus the periodontal disease is controlled again., (© 2021. The Author(s).)

Background: Type 2 diabetes mellitus (T2DM) and periodontitis (P) commonly occur as comorbidities, but the commonalities in the genetic makeup of affected individuals is largely unknown. Since dyslipidemia is a frequent condition in these individuals, we investigate the association of genomic variations in genes involved in lipid metabolism with periodontal, glycemic, lipid profiles, and the association with periodontitis and T2DM (as comorbidities)., Methods: Based on clinical periodontal examination and biochemical evaluation, 893 subjects were divided into T2DM+P (T2DM subjects also affected by periodontitis, n = 205), periodontitis ( n = 345), and healthy ( n = 343). Fourteen single-nucleotide polymorphisms (SNPs) were investigated: LDLR gene (rs5925 and rs688), APOB (rs676210, rs1042031, and rs693), ABCC8 (rs6544718 and 6544713), LPL (rs28524, rs3735964, and rs1370225), HNF1A (rs2650000), APOE (rs429358 and rs7412), and HNF4A (rs1800961). Multiple linear and logistic regressions (adjusted for covariates) were made for all populations and stratified by sex and smoking habits., Results: Individuals carrying APOB -rs1042031-CT (mainly women and never smokers) had a lower risk of developing periodontitis and T2DM (T2DM+P); altogether, this genotype was related with healthier glycemic, lipid, and periodontal parameters. Significant disease-phenotype associations with gene-sex interaction were also found for carriers of APOB -rs1676210-AG, HNF4A -rs1800961-CT, ABCC8 -rs6544718-CT, LPL -rs13702-CC, and LPL -rs285-CT., Conclusions: Polymorphisms in lipid metabolism genes are associated with susceptibility to T2DM-periodontitis comorbidities, demonstrating gene-sex interaction. The APOB -rs1042031 was the most relevant gene marker related to glucose and lipid metabolism profiles, as well as with obesity and periodontitis., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2021 Ingra G. Nicchio et al.)

Objectives: The present study aimed to compare two different models of orthodontic tooth movement (OTM) in rats by evaluating tooth movement efficiency and periodontal tissues remodelling., Design: Fifteen animals were randomly distributed into 3 groups: control group (untreated); ligature appliance (LA) as experimental OTM using a closed coil spring fixed around maxillary first molar by steel ligature; occlusal appliance (OA) as experimental OTM using a closed coil spring attached on the occlusal surface of the maxillary first molar. After 15 days, all animals were euthanized, and the maxilla of each animal was collected for qPCR, micro-computed tomography, and histological analyses., Results: Interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha gene expressions were significantly upregulated in the animals of the LA group as compared to the other groups. No significant difference was observed in tooth displacement between both methods. The LA group presented higher linear bone loss and lower values of bone volume fraction, bone mineral density, trabecular number and increased values of trabecular separation compared to the other groups. The birefringent collagen content in the tension side of the periodontal ligament contained significantly lower collagen content in the LA group than in the control group. Furthermore, on the pressure side, the collagen content was significantly lower in the LA and OA groups than in the control group., Conclusions: The OA group presented little or no deleterious effect on periodontal tissues compared to the LA group, suggesting its use may be more reliable for OTM induction in rats for 15 days., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

In the last decades, Periodontal Regeneration has been one of the most discussed topics in Periodontics, attracting the attention of researchers and clinicians. This can be justified by the evident and continuous progress observed in the field, characterized by a better understanding of the biological mechanisms involved, significant improvement of operative and technical principles, and the emergence of a wide range of biomaterials available for this purpose. Together, these aspects put the theme much in evidence in the search for functional and esthetic therapeutic solutions for periodontal tissue destruction. Despite the evident evolution, periodontal regeneration may be challenging and require the clinician to carefully evaluate each case before making a therapeutic decision. With a critical reassessment of the clinical and preclinical literature, the present study aimed to discuss the topic to answer whether Periodontal Regeneration is still a goal in clinical periodontology. The main aspects involved in the probability of success or failure of regenerative approaches were considered. A greater focus was given to intrabony and furcation defects, clinical conditions with greater therapeutic predictability. Aspects such as more appropriate materials/approaches, long-term benefits and their justification for a higher initial cost were discussed for each condition. In general, deep intrabony defects associated with residual pockets and buccal/lingual class II furcation lesions have predictable and clinically relevant results. Careful selection of the case (based on patient and defect characteristics) and excellent maintenance are essential conditions to ensure initial and long-term success.

Objective: Genome-wide association studies (GWAS) and literature have identified polymorphisms in the KCNJ11, HNF1A, IRS1, TCF7L2, CDKAL1, CDKN2B, RPSAP52, GPR45 HHEX, IL18, and RUNX2 genes associated with type 2 diabetes mellitus (T2DM) and/or periodontitis (P) in diverse populations, and we sought to evaluate them as genetic risk variants for these diseases in the Brazilian population., Material and Methods: Periodontal, glycemic, and lipid data were obtained from 931 individuals divided into: control (n = 334), periodontitis (P; n = 358), and periodontitis associated with T2DM (P + T2DM; n = 239). After genotyping, associations between polymorphisms and pathologies were tested by multiple logistic and linear regressions, adjusting for age, sex, and smoking habits., Results: Considering the studied subjects, the increased risk to develop periodontitis in the periodontitis P + T2DM group was found for HNF1A-rs7957197-TA, CDKAL1-rs7754840-CG, RPSAP52-rs1531343-GC, TCF7L2-rs7903146-TT, and CDKN2B-rs7018475-GG. The association of these genetic variants for TCF7L2 and CDKN2B was confirmed for female, never smokers, and poorly controlled P + T2DM. CDKN2B-rs7018475 was associated with worse glycemic condition and periodontal parameters., Conclusion: These five reported genetic variants were associated in the studied Southeastern Brazilian population as genetic risk variants of periodontitis and T2DM associated to periodontitis as comorbidity. Gene-phenotype associations with sex and smoking habits and the CDKN2B-rs7018475 with the poor glycemic control and more severe periodontal conditions should be further investigated., Clinical Relevance: Polymorphisms in the CDKAL1-rs7754840, HNF1A-rs7957197, RPSAP52-rs1531343, TCF7L2-rs7903146, and CDKN2B-rs7018475 might predispose to periodontitis and T2DM associated with periodontitis. These findings may be useful in public health genomics and future advanced clinical practice, since genetic carriage can be measured before disease onset, being of potential great benefit for treatment planning and prognosis in early disease stages.

Objectives: The aim of this study was to evaluate the behavior of rat bone marrow stem cells seeded on a Ti-15Mo alloy surface modified by laser-beam irradiation followed by calcium phosphate deposition., Materials and Methods: A total of four groups were evaluated: polished commercially pure titanium (cpTi): Ti-P; laser irradiation + calcium phosphate deposition on cpTi: Ti-LCP; polished Ti-15Mo alloy: Ti15Mo-P; and laser irradiation + calcium phosphate deposition on Ti-15Mo alloy: Ti15Mo-LCP. Before and after laser irradiation and calcium phosphate deposition on the surfaces, physicochemical and morphological analyses were performed: Scanning Electron Microscopy (SEM) and Energy Dispersive Spectroscopy (EDX). The wettability of the samples was evaluated by contact angle measurement. In addition, the behavior of osteoblast-like cells to these surfaces was evaluated for cell morphology, adhesion, proliferation and viability, evaluation of alkaline phosphatase formation and gene expression of osteogenesis markers., Results: Surfaces wet-abrade with grit paper (P) showed oriented groves, while the laser irradiation and calcium phosphate deposition (LCP) produced porosity on both cpTi and Ti15Mo alloy groups with deposits of hydroxyapatite (HA) crystals (SEM). EDX showed no contamination after surface modification in both metal samples. A complete wetting was observed for both LCP groups, whereas P surfaces exhibited high degree of hydrophobicity. There was a statistical difference in the intragroup comparison of proliferation and viability (p < 0.05). The ALP activity showed higher values in the Ti15Mo alloy at 10 days of culture. The gene expression of bone related molecules did not present significant differences at 7 and 14 days among different metals and surface treatments., Conclusion: Ti15-Mo seems to be an alternative alloy to cpTi for dental implants. Surface treatment by laser irradiation followed by phosphate deposition seems to positively interact with bone cells., Clinical Relevance: Ti-15Mo alloy surface modified by laser-beam irradiation followed by calcium phosphate deposition may improve and accelerate the osseointegration process of dental implants.

Background: Bioinformatic tools and genome-wide association studies (GWAS) have led to comprehensive identification of single nucleotide polymorphisms (SNPs) associated with periodontitis in diverse populations. Here we aimed to detect and validate the association of seven SNPs as genetic markers of susceptibility to periodontitis in a Brazilian population., Methods: This case-control study assessed complete periodontal parameters of 714 subjects with periodontal status classified as healthy/mild periodontitis (n = 356) and moderate/severe periodontitis (n = 358). Genotyping for rs187238, rs352140, rs1360573, rs2521634, rs3811046, rs3826782, and rs7762544 SNPs were evaluated. Genetic-phenotype associations, and sex or smoking effects of SNPs on periodontitis were tested using multiple logistic regressions adjusted for covariates., Results: The rs2521634-AA (close to NPY gene) presented increased risk for severe periodontitis (OR = 2.34; 95% CI = 1.19-4.59). The rs3811046-GG (IL37 gene) demonstrated increased risk for moderate periodontitis (OR = 2.58; 95% CI = 1.28-5.18). Higher risk for moderate periodontitis was found in male with rs7762544-AG close to NCR2 gene. The rs352140-TT in the TLR9 gene proved to be associated with lower risk to severe periodontitis in men. The rs2521634-AA was associated with higher percentage of interproximal probing pocket depth (P = .004)., Conclusions: This is the first evidence of validation in a Brazilian population of genetic markers of periodontitis previously investigated by GWAS and bioinformatics studies. SNPs in the NPY, IL37, and NCR2 genes were associated with susceptibility to moderate or severe periodontitis; whereas the TLR9 marker was associated with lower chance to develop severe periodontitis. Those SNPs had sex- and smoking-habit-specific effects on periodontitis; reinforcing the genetic profile predisposing to periodontitis., (© 2020 American Academy of Periodontology.)

Introduction: Orthodontic movement triggers a sequence of cellular and molecular events that may be affected by different systemic conditions. This study evaluated the effect of obesity on rat periodontal tissue remodeling induced by mechanical orthodontic force., Methods: Thirty-two Holtzman rats were distributed into 4 groups: control, obesity induction (O), orthodontic movement (M), and obesity induction and orthodontic movement (OM). Obesity was induced by a high-fat diet for 90 days. After 15 days of orthodontic movement, the animals were killed. Obesity induction was confirmed by animal body weight, adipose tissue weight, and serologic analysis. Periodontal tissue remodeling was evaluated using microcomputed tomography and histologic analysis. The gene expression of adipokines and cytokines in gingival tissues was evaluated., Results: An increase in body and adipose tissue weight was observed in the obesity induction groups. The O group presented an increase in lipids and blood glucose. The OM group showed a decrease in bone volume fraction and bone mineral density compared with all other groups and a tendency for more rapid tooth movement than the M group. The OM group showed a higher quantity of inflammatory cells and higher Mmp1 expression than the O group. The O and OM groups showed higher Nampt expression than the control group and lower Nampt expression than the M group., Conclusions: Obesity modulates periodontal tissue remodeling during orthodontic movement and results in more inflammation and bone loss than in nonobese animals., (Copyright © 2020 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Rehabilitation of atrophic maxilla with dental implants is still a challenge in clinical practice especially in cases of alveolar bone resorption due to peri-implantitis and pneumatization of the maxillary sinuses. Several surgical approaches have been employed to reconstruct the lost tissues allowing the proper tridimensional position of the implants. In this context, the aim of this case report is to describe a surgical and prosthetic approach to fully rehabilitate the atrophic maxilla with dental implants. The patient presented with unsatisfactory functional and esthetical implant-supported prosthesis with some of the implants already lost by peri-implantitis. The remaining three implants were also affected by peri-implantitis. Reversal prosthetic planning was performed, and a provisional prosthesis was fabricated and anchored in two short implants. Sinus floor augmentation procedure and onlay bone graft were then accomplished. After a healing period of 8 months, digital-guided surgery approach was performed to place the implants. Finally, a definitive prosthesis was installed. One-year follow-up has revealed stabilization of the bone tissue level, successful osseointegration, and a pleasant esthetic and functional result. A proper diagnosis and careful planning play an important role to enhance precision and to achieve patient esthetic and functional outcomes., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2021 Angélica Letícia Reis Pavanelli et al.)

Phytocystatins are endogenous cysteine-protease inhibitors present in plants. They are involved in initial germination rates and in plant defense mechanisms against phytopathogens. Recently, a new phytocystatin derived from sweet orange, CsinCPI-2, has been shown to inhibit the enzymatic activity of human cathepsins, presenting anti-inflammatory potential and pro-osteogenic effect in human dental pulp cells. The osteogenic potential of the CsinCPI-2 protein represents a new insight into plants cysteine proteases inhibitors and this effect needs to be better addressed. The aim of this study was to investigate the performance of pre-osteoblasts in response to CsinCPI-2, mainly focusing on cell adhesion, proliferation and differentiation mechanisms. Together our data show that in the first hours of treatment, protein in CsinCPI-2 promotes an increase in the expression of adhesion markers, which decrease after 24 h, leading to the activation of Kinase-dependent cyclines (CDKs) modulating the transition from G1 to S phases cell cycle. In addition, we saw that the increase in ERK may be associated with activation of the differentiation profile, also observed with an increase in the B-Catenin pathway and an increase in the expression of Runx2 in the group that received the treatment with CsinCPI-2.

Objective: The aim of the present study was to evaluate the expressions of CXCL5, CXCL8, and CXCL10 in periodontal cells and tissues in response to microbial signals and/or biomechanical forces., Methods: Human gingival biopsies from inflamed and healthy sites were used to examine the chemokine expressions and protein levels by real-time PCR and immunohistochemistry. The chemokines were also investigated in gingival biopsies from rats submitted to experimental periodontitis and/or tooth movement. Furthermore, chemokine levels were determined in human periodontal fibroblasts stimulated by the periodontopathogen Fusobacterium nucleatum and/or constant tensile forces (CTS) by real-time PCR and ELISA. Additionally, gene expressions were evaluated in periodontal fibroblasts exposed to F. nucleatum and/or CTS in the presence and absence of a MAPK inhibitor by real-time PCR., Results: Increased CXCL5, CXCL8, and CXCL10 levels were observed in human and rat gingiva from sites of inflammation as compared with periodontal health. The rat experimental periodontitis caused a significant (p<0.05) increase in alveolar bone resorption, which was further enhanced when combined with tooth movement. In vitro, F. nucleatum caused a significant upregulation of CXCL5, CXCL8, and CXCL10 at 1 day. Once the cells were exposed simultaneously to F. nucleatum and CTS, the chemokines regulation was significantly enhanced. The transcriptional findings were also observed at protein level. Pre-incubation with the MEK1/2 inhibitor significantly (p<0.05) inhibited the stimulatory actions of F. nucleatum either alone or in combination with CTS on the expression levels of CXCL5, CXCL8, and CXCL10 at 1d., Conclusions: Our data provide original evidence that biomechanical strain further increases the stimulatory actions of periodontal bacteria on the expressions of these chemokines. Therefore, biomechanical loading in combination with periodontal infection may lead to stronger recruitment of immunoinflammatory cells to the periodontium, which might result in an aggravation of periodontal inflammation and destruction., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Few studies evaluate interrelationships between periodontitis (P) and Type 2 Diabetes Mellitus (T2DM). The aim of this study is to investigate the genetic susceptibility to periodontitis alone, or concomitant with T2DM (as comorbidities), analyzing single nucleotide polymorphisms (SNPs) in the Interleukin 17 alpha (IL17A) gene, considering the biochemical profile and smoking habits on the subjects' periodontal status. We investigated 879 individuals divided into: T2DM subjects also affected by severe or moderate periodontitis (T2DM-P, n = 199); non-diabetics with severe or moderate periodontitis (PERIODONTITIS, n = 342); and healthy subjects (HEALTHY, n = 338). Subjects underwent complete periodontal examination, history of smoking habits, glycemic and lipid biochemical evaluation. DNA from buccal cells was utilized to genotype the SNPs rs2275913, rs3819024 and rs10484879. The impact of the subjects' biochemical profile was analyzed in their periodontal status. Each SNP was analyzed independently, and as haplotypes, by multiple logistic regressions, adjusted for covariates, and also stratifying the groups by age, sex and smoking habits. Independently of the periodontitis degree, poorly-controlled T2DM subjects showed worse glycemic and lipid profile. Multiple logistic regressions demonstrated that smokers and former-smokers carrying the GG genotype of rs3819024 seemed to have higher risk for T2DM-Periodontitis (OR = 6.33; 95% CI = 1.26-31.77, p = 0.02), and mainly for T2DM alone (OR = 5.11; 95% CI = 1.37-19.06, p = 0.01), than never smokers. We found the potential effect of smoking habits in the association of IL17A-rs3819024-GG with diseased phenotypes. Because the observed wide confidence intervals, further studies enrolling larger populations, and SNPs' functional evaluations are needed to better understand our findings.

Objective: To assess whether single nucleotide polymorphisms (SNPs) in the IL10, IL1A, IL1B, IL4, TNFA, IL6, OPG, RANK, and RANKL genes, "classically" related with periodontitis, could be associated with susceptibility to T2DM, and also with both diseases concomitantly., Background: There are common pathogenic mechanisms in type 2 diabetes mellitus (T2DM) and periodontitis, but the knowledge of the genetic aspect of this is limited. In patients affected by concomitant T2DM and periodontitis, whose incidence is increasing, there is scarce information regarding the gene-phenotype association, including whether there are genes able to influence both diseases as comorbidities., Methods: Periodontal clinical parameters and biochemical profile (Insulin, Fasting Glycemia, HbA1c, Triglycerides, Total Cholesterol, HDL-cholesterol, and LDL-cholesterol) data were obtained from 894 individuals divided into following three groups: Healthy (H; n = 347), Periodontitis (P; n = 348), and Periodontitis + T2DM (P + T2DM; n = 199). DNA from oral epithelial cells was collected for genotyping. Associations between SNPs and pathologies were tested by multiple logistic regression models, adjusting for age, sex, and smoking habits. We also investigated whether there are sex or smoking effects of each SNP in these phenotypes., Results: The rs1143634-GA (IL1B) SNP showed significantly less likely to develop P + T2DM for all population and mainly for women (adjusted OR = 0.37, 95% CI = 0.16-0.88), while women carrying the rs224320 CT (IL4) were more susceptible to develop P + T2DM (adjusted OR = 1.81, 95% CI = 1.04-3.15). Men carrying the rs1800795-CC (IL6) genotype were less likely to develop T2DM (adjusted OR = 0.12, 95% CI = 0.02-0.70, P = .01)., Conclusions: Some SNPs in the IL1B, IL4, and IL6 genes demonstrated sex-influenced association with concomitant periodontitis and T2DM, increasing the evidence of a common genetic component between these diseases and contributing with the understanding of their common pathogenic mechanisms., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Aim: Type 2 Diabetes Mellitus (T2DM) and Periodontitis (P) are prevalent multifactorial disorders worldwide, sharing a bidirectional relationship influenced by the genetic susceptibility of the host immune system. We investigated whether SNPs in the Interleukin 8 (IL8, alias CXCL8) gene could be associated with T2DM and Periodontitis., Methods: Genomic DNA was obtained from 874 Brazilian individuals divided into: Healthy group (n = 307), Periodontitis group (n = 334), and individuals affected by both T2DM and Periodontitis (T2DM&#95;P) group (n = 233). The SNPs -251(T>A) rs4073, +396(T>G) rs2227307 and +781(C>T) rs2227306 were genotyped by TaqMan®. Multiple logistic regressions were used to determine the degree of association between polymorphisms (and haplotypes) with periodontitis and T2DM adjusted for known confounders., Results: The additive model revealed that the heterozygous AT(-251), GT(+396) and CT(+781) genotypes showed a lower risk for the diseased phenotypes, and carriers of the TTC/TTC haplotype were significantly susceptible to T2DM and Periodontitis concomitantly, as well to isolated Periodontitis (mainly the severe form)., Conclusions: We concluded, for the first time, that these functional CXCL8 SNPs, and the homozygous TTC haplotype are relevant genetic factors for T2DM and Periodontitis as comorbidities, as well as for severe Periodontitis susceptibility in Brazilian population., Competing Interests: Declaration of competing interest The authors have stated explicitly that there are no conflicts of interest in connection with this article., (Copyright © 2020 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Objective: It is increasingly common to find patients affected by a combination of type 2 diabetes mellitus (T2DM), dyslipidemia (DLP) and periodontitis (PD), which are chronic inflammatory diseases. More studies able to capture unknown relationships among these diseases will contribute to raise biological and clinical evidence. The aim of this study was to apply association rule mining (ARM) to discover whether there are consistent patterns of clinical features (CFs) and differentially expressed genes (DEGs) relevant to these diseases. We intend to reinforce the evidence of the T2DM-DLP-PD-interplay and demonstrate the ARM ability to provide new insights into multivariate pattern discovery., Methods: We utilized 29 clinical glycemic, lipid and periodontal parameters from 143 patients divided into five groups based upon diabetic, dyslipidemic and periodontal conditions (including a healthy-control group). At least 5 patients from each group were selected to assess the transcriptome by microarray. ARM was utilized to assess relevant association rules considering: (i) only CFs; and (ii) CFs+DEGs, such that the identified DEGs, specific to each group of patients, were submitted to gene expression validation by quantitative polymerase chain reaction (qPCR)., Results: We obtained 78 CF-rules and 161 CF+DEG-rules. Based on their clinical significance, Periodontists and Geneticist experts selected 11 CF-rules, and 5 CF+DEG-rules. From the five DEGs prospected by the rules, four of them were validated by qPCR as significantly different from the control group; and two of them validated the previous microarray findings., Conclusions: ARM was a powerful data analysis technique to identify multivariate patterns involving clinical and molecular profiles of patients affected by specific pathological panels. ARM proved to be an effective mining approach to analyze gene expression with the advantage of including patient's CFs. A combination of CFs and DEGs might be employed in modeling the patient's chance to develop complex diseases, such as those studied here., Competing Interests: The authors have declared that no competing interests exist.

Objectives: This study was established to investigate whether the chemokines CXCL1, CCL2, and CCL5 are produced in periodontal cells and tissues and, if so, whether their levels are regulated by microbial and/or mechanical signals., Materials and Methods: The chemokine expression and protein levels in gingival biopsies from patients with and without periodontitis were analyzed by RT-PCR and immunohistochemistry. The chemokines were also analyzed in gingival biopsies from rats subjected to experimental periodontitis and/or orthodontic tooth movement. Additionally, chemokine levels were determined in periodontal fibroblasts exposed to the periodontopathogen Fusobacterium nucleatum and mechanical forces by RT-PCR and ELISA., Results: Higher CXCL1, CCL2, and CCL5 levels were found in human and rat gingiva from sites of periodontitis as compared with periodontally healthy sites. In the rat experimental periodontitis model, the bacteria-induced upregulation of these chemokines was significantly counteracted by orthodontic forces. In vitro, F. nucleatum caused a significant upregulation of all chemokines at 1 day. When the cells were subjected simultaneously to F. nucleatum and mechanical forces, the upregulation of chemokines was significantly inhibited. The transcriptional findings were paralleled at protein level., Conclusions: This study provides original evidence in vitro and in vivo that the chemokines CXCL1, CCL2, and CCL5 are regulated by both microbial and mechanical signals in periodontal cells and tissues. Furthermore, our study revealed that biomechanical forces can counteract the stimulatory actions of F. nucleatum on these chemokines., Clinical Relevance: Mechanical loading might aggravate periodontal infection by compromising the recruitment of immunoinflammatory cells.

Previous studies have shown that topical application of lectin Artin-M accelerates wound healing in the rat oral mucosa. The aim of this study was to evaluate, by means of histology and immunohistochemistry (IHC) the effects of Artin-M on wound healing in the palatal mucosa in dogs. Three full thickness wounds of 6 mm diameter were surgically created in the palatal mucosa of twenty dogs and randomly divided into three groups according to one of the treatment assigned: Group C-Control (coagulum); Group A-Artin-M gel; Group V-Vehicle (carboxymethylcellulose 3%). Each animal received all the three experimental treatments. Afterwards, four animals were killed at 2, 4, 7, 14 and 21 days post-surgery. Wounded areas were photographed and scored for macroscopic evaluation. Biopsies were harvested and used for descriptive histological analysis, proliferating cell nuclear antigen IHC and measurement of myeloperoxidase activity. The results demonstrated faster wound closure in group A in comparison to the other groups in all the periods evaluated. Histological analyses exhibited improved re-epithelialization and collagen fiber formation resulting in faster maturation of granulation tissue in group A compared to the other groups by day 14. Treatment with Artin-M gel significantly induced cell proliferation and increased volumetric density of fibroblasts at day 2 and 4 (p < 0.05). Neutrophil infiltration in group A was significantly higher than the other groups (p < 0.05) at the same time points. Collectively, our findings demonstrated that Artin-M may potentially favor wound healing on palatal mucosa lesions via recruitment of neutrophils and promotion of cell proliferation.

This study evaluated by micro-computed tomography (μCT) the filling ability in curved root canals, besides the flow of AH Plus (AHP) and Neo MTA Plus (NMTAP) sealers using different methodologies. Mandibular molars mesial roots with two root canals and degree of curvature between 20° and 40° were selected. The specimens were prepared with the ProDesign R system up to size 35.05 and were filled with the sealers by a continuous wave of condensation technique, Thermo Pack II (n=12). The teeth were scanned using μCT after root canal preparation and obturation. The volumetric percentage of filling material and voids were calculated. Flow was evaluated based on ISO 6876/2012 (n=10). Flow and filling were also evaluated in μCT using a glass plate with a central cavity and four grooves from the central cavity (n=6). Flow was linearly calculated into the grooves. The central cavity filling (CCF) and lateral cavity filling (LCF) were calculated in mm³. Data were submitted to non-paired t test with a significance threshold at 5%. The percentage of filling and voids between the root canals filled with AHP or NMTAP was similar (p>0.05). NMTAP presented the lowest flow in conventional test (p<0.05). Using μCT, sealers had similar CCF, LCF and linear flow (p>0.05). In conclusion, NMTAP and AHP had similar filling ability in curved mesial root canals of mandibular molars without presence of isthmus. Although AHP presented better flow than NMTAP using ISO methodology, there was no difference between these materials regarding volumetric filling when evaluated by μCT.

Objective: The aim of this study was to compare the periodontal tissue changes resulting from different methods of orthodontic tooth extrusion in dogs., Materials and Methods: Notches were surgically prepared in the root surface at the bone crest level of the first premolars of mongrel dogs. After 37 days, extrusion of the first lower and upper premolars was randomly performed by 3 different methods: conventional orthodontic extrusion (OE); open flap debridement performed immediately before orthodontic extrusion (OF); and orthodontic extrusion associated with weekly fiberotomy and scaling (FS). For all groups, extrusion was performed for 21 days followed by one-month retention and sacrifice. Periodontal parameters, descriptive histology, and histomorphometric analyses were performed at the end of the experimental period., Results: The median extrusion was 2.25 in the fiberotomy group, 2.0 mm in the open flap group and 1.0 mm in the orthodontic extrusion group with no significant differences between groups. The highest distance between reference notch and bone crest was observed in the fiberotomy group (p < 0.05). Histologically, radicular resorption repaired with cellular cementum was detected in all groups., Conclusions: Tooth extrusion was successfully achieved with all of the different methods of orthodontic tooth extrusion with no statistical significance between techniques. The fiberotomy approach was effective in avoiding coronal displacement of periodontal tissues. Fiberotomy associated with scaling should be indicated if the objective of the treatment is extrusion without periodontal tissue displacement., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Resistin, a proinflammatory adipokine, is elevated in many inflammatory diseases. However, little is known about its performance in periodontitis. The present study is aimed at evaluating resistin expression and synthesis in periodontal cells and tissues under inflammatory/microbial stress in addition to its effects on the periodontium. In vivo, 24 male rats were randomly divided into two groups: control and ligature-induced periodontal disease. After 6 and 12 days, animals were sacrificed to analyze gene expression of adipokines, bone loss, inflammation, and resistin synthesis. In vitro, human periodontal ligament (PDL) fibroblasts were used to evaluate the expression of resistin after inflammatory stimuli. In addition, PDL fibroblasts were exposed to resistin to evaluate its role on soft and hard tissue metabolism markers. The periodontitis group demonstrated significant bone loss, an increase in the number of inflammatory cells and vascular structures, an increase in resistin expression and synthesis, and a decrease in the expression of adiponectin, leptin, and its functional receptor. PDL fibroblasts showed a significant increase in resistin expression and synthesis in response to the inflammatory stimulus by IL-1 β . Resistin induced an increase in cytokine expression and a decrease in the regulation of some hard tissue and matrix formation genes in PDL fibroblasts. These data indicate that resistin is produced by periodontal cells and tissues, and this effect is enhanced by inflammatory stimuli. Moreover, resistin seems to interfere with soft and hard tissue metabolism during periodontitis by reducing markers related to matrix formation and bone tissue., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2020 Andressa V. B. Nogueira et al.)

Purpose: Orthodontic treatment is based on the principle of force application to teeth and subsequently to the surrounding tissues and periodontal cells. Sequestosome 1 (SQSTM1) is a well-known marker for autophagy, which is an important cellular mechanism of adaptation to stress. The aim of this study was to analyze whether biomechanical loading conditions regulate SQSTM1 in periodontal cells and tissues, thereby providing further information on the role of autophagy in orthodontic tooth movement., Methods: Periodontal ligament (PDL) fibroblasts were exposed to cyclic tensile strain of low magnitude (3%, CTSL), and the regulation of autophagy-associated targets was determined with an array-based approach. SQSTM1 was selected for further biomechanical loading experiments with dynamic and static tensile strain and assessed via real-time polymerase chain reaction (RT-PCR) and immunoblotting. Signaling pathways involved in SQSTM1 activation were analyzed by using specific inhibitors, including an autophagy inhibitor. Finally, SQSTM1 expression was analyzed in gingival biopsies and histological sections of rats in presence and absence of orthodontic forces., Results: Multiple autophagy-associated targets were regulated by CTSL in PDL fibroblasts. All biomechanical loading conditions tested increased the SQSTM1 expression significantly. Stimulatory effects of CTSL on SQSTM1 expression were diminished by inhibition of the c‑Jun N‑terminal kinase (JNK) pathway and of autophagy. Increased SQSTM1 levels after CTSL were confirmed by immunoblotting. Orthodontic force application also led to significantly elevated SQTSM1 levels in the gingiva and PDL of treated animals as compared to control., Conclusions: Our in vitro and in vivo findings provide evidence of a role of SQSTM1 and thereby autophagy in orthodontic tooth movement.

Objective To compare two corticotomy surgical protocols in rats to verify whether they alter conventional orthodontic movement. Methodology Sixty Wistar rats were divided into three groups - orthodontic movement (CG), orthodontic movement and corticotomy (G1) and orthodontic movement with corticotomy and decortication (G2) - and euthanized after 7 and 14 days. Tooth movement (mm), bone volume fraction and bone volume ratio to total volume (BV/TV), and bone mineral density (BMD) were evaluated by micro-CT. The total amount of bone was measured in square millimeters and expressed as the percentage of bone area in the histomorphometry. The number of positive TRAP cells and RANK/RANKL/OPG interaction were also investigated. Results Day 14 showed a statistically significant difference in orthodontic tooth movement in CG compared with G1 (7.52 mm; p=0.009) and G2 (7.36 mm; p=0.016). A micro-CT analysis revealed a difference between CG, G1 and G2 regarding BV/TV, with G1 and G2 presenting a lower BV/TV ratio at 14 days (0.77 and 0.73 respectively); we found no statistically significant differences regarding BMD. There was a difference in the total amount of bone in the CG group between 7 and 14 days. At 14 days, CG presented a significantly higher bone percentage than G1 and G2. Regarding TRAP, G2 had more positive cells at 7 and 14 days compared with CG and G1. Conclusion Corticotomy accelerates orthodontic movement. Decortication does not improve corticotomy efficiency.

Cystatins are natural inhibitors of cysteine peptidases. Recently, cystatins derived from plants, named phytocystatins, have been extensively studied. Among them, CsinCPI-2 proteins from Citrus sinensis were identified and recombinantly produced by our group. Thus, this study described the recombinant expression, purification, and inhibitory activity of this new phytocystatin against human cathepsins K and B and assessed the anti-inflammatory effect of CsinCPI-2 in vitro in mouse and in vivo in rats. In addition, the pro-osteogenic effect of CsinCPI-2 was investigated in vitro. The inflammatory response of mouse macrophage cells stimulated with P. gingivalis was modulated by CsinCPI-2. The in vitro results showed an inhibitory effect (p < 0.05) on cathepsin K, cathepsin B, IL-1β, and TNF-α gene expression. In addition, CsinCPI-2 significantly inhibited in vivo the activity of TNF-α (p < 0.05) in the blood of rats, previously stimulated by E. coli lipopolysaccharide (LPS). CsinCPI-2 had a pro-osteogenic effect in human dental pulp cells, demonstrated by the increase in alkaline phosphatase (ALP) activity, deposition of mineralized nodules, and the gene expression of the osteogenic markers as bone morphogenetic protein 2 (BMP-2), runt-related transcription factor 2 (Runx-2), ALP, osteocalcin, and bone sialoprotein (BSP). These preliminary studies suggested that CsinCPI-2 has a potential anti-inflammatory, and at the same time, a pro-osteogenic effect. This may lead to new therapies for the control of diseases where inflammation plays a key role, such as periodontal disease and apical periodontitis., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Specialized proresolving mediators (SPRM), which arise from n-3 long-chain polyunsaturated fatty acids (n-3FA), promote resolution of inflammation and may help to prevent progression of an acute inflammatory response into chronic inflammation in patients with arthritis. Thus, this study is aimed at determining whether systemic RvE1 treatment reduces arthritis onset and severity in murine collagen-induced arthritis (CIA) and spontaneous cytokine production by human rheumatoid arthritis (RA) synovial explants. 10-week-old DBA1/J male mice were subjected to CIA and treated systemically with 0.1  μ g RvE1, 1  μ g RvE1, 5 mg/kg anti-TNF (positive control group), PBS (negative control group), or with a combination of 1  μ g of RvE1 plus 5 mg/kg anti-TNF using prophylactic or therapeutic strategies. After CIA immunization, mice were treated twice a week by RvE1 or anti-TNF for 10 days. Arthritis development was assessed by visual scoring of paw swelling and histology of ankle joints. Moreover, human RA synovial explants were incubated with 1 nM, 10 nM, or 100 nM of RvE1, and cytokine levels (IL-1 β , IL-6, IL-8, IL-10, INF- γ , and TNF- α ) were measured using Luminex bead array. CIA triggered significant inflammation in the synovial cavity, proteoglycan loss, and cartilage and bone destruction in the ankle joints of mice. Prophylactic and therapeutic RvE1 regimens did not ameliorate CIA incidence and severity. Anti-TNF treatment significantly abrogated signs of joint inflammation, bone erosion, and proteoglycan depletion, but additional RvE1 treatment did not further reduce the anti-TNF-mediated suppression of the disease. Treatment with different concentrations of RvE1 did not decrease the expression of proinflammatory cytokines in human RA synovial explants in the studied conditions. Collectively, our findings demonstrated that RvE1 treatment was not an effective approach to treat CIA in DBA1/J mice in both prophylactic and therapeutic strategies. Furthermore, no effects were noticed when human synovial explants were incubated with different concentrations of RvE1., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2019 Rafael Scaf de Molon et al.)

The association between rheumatoid arthritis (RA) and periodontal disease (PD) has been the focus of numerous investigations driven by their common pathological features. RA is an autoimmune disease characterized by chronic inflammation, the production of anti-citrullinated proteins antibodies (ACPA) leading to synovial joint inflammation and destruction. PD is a chronic inflammatory condition associated with a dysbiotic microbial biofilm affecting the supporting tissues around the teeth leading to the destruction of mineralized and non-mineralized connective tissues. Chronic inflammation associated with both RA and PD is similar in the predominant adaptive immune phenotype, in the imbalance between pro- and anti-inflammatory cytokines and in the role of smoking and genetic background as risk factors. Structural damage that occurs in consequence of chronic inflammation is the ultimate cause of loss of function and disability observed with the progression of RA and PD. Interestingly, the periodontal pathogen Porphyromonas gingivalis has been implicated in the generation of ACPA in RA patients, suggesting a direct biological intersection between PD and RA. However, more studies are warranted to confirm this link, elucidate potential mechanisms involved, and ascertain temporal associations between RA and PD. This review is mainly focused on recent clinical and translational research intends to discuss and provide an overview of the relationship between RA and PD, exploring the similarities in the immune-pathological aspects and the possible mechanisms linking the development and progression of both diseases. In addition, the current available treatments targeting both RA and PD were revised.