Impacto do uso sistêmico de estatinas e de bisfosfonatos nos tecidos periodontais: revisão narrativa / Impact of the systemic use of statins and bisphosphonates in the periodontal tissues: narrative review

Introdução: A literatura tem apontado uma possível relação entre diversas condições sistêmicas e as doenças periodontais. Dentro das doenças sistêmicas que podem gerar o uso crônico de medicamentos, com potencial associação com as doenças periodontais, destacam-se a hipercolesterolemia e o uso de estatinas; e as doenças do metabolismo ósseo e o uso de bisfosfonatos. Objetivo: Dessa maneira, o presente estudo objetivou revisar a literatura sobre o efeito das estatinas e dos bisfosfonatos nos parâmetros clínicos e radiográficos periodontais de indivíduos adultos. Resultados: Apenas estudos observacionais em humanos foram incluídos. Um estudo mostrou que, em pacientes que apresentam doença periodontal e usam estatina, houve 37% menos bolsas periodontais (profundidade de sondagem ≥4mm) quando comparadas aos que não utilizam a medicação, além de apresentarem menor índice de carga inflamatória e menor perda de inserção clínica. Em relação aos bisfosfonatos em indivíduos com doenças que envolvem o metabolismo ósseo, sugere-se que a utilização do fármaco tem obtido resultados positivos nos parâmetros periodontais, como menores sinais clínicos de inflamação gengival, menor profundidade de sondagem, menor perda de inserção clínica e maior nível de osso alveolar, quando comparados aos que nunca realizam essa terapia. Conclusão: Dessa forma, as estatinas e os bisfosfonatos apresentam efeitos promissores, em pacientes sob tratamento para suas respectivas condições sistêmicas, na melhoria dos parâmetros periodontais, porém é importante salientar que são necessários mais estudos sobre o assunto para melhor entender os reais efeitos a longo prazo do uso desses fármacos.(AU)

Introduction: The literature showed a possible relationship between several systemic conditions and periodontal diseases. Within the systemic diseases that can generate the chronic use of these drugs, potentially related with periodontal diseases, it may be cited the hypercholesterolemia and the use of statins; and bone metabolism diseases and the use of bisphosphonates. Objective: In this sense, the present study aimed to review the literature about the effect of statins and bisphosphonates in the periodontal parameters of adults individuals. Results: Only observational studies in humans were included. A study showed that, in patients with periodontal disease and users of statins, there 37% fewer periodontal pockets (probing depth ≥4mm) when compared to those who do not use the medication, as well as having a lower rate of inflammatory burden and less loss of clinical insertion. Regarding the bisphosphonates in individuals diagnosed with diseases involving bone metabolism, it was suggested that the use of the drug has obtained positive results in periodontal parameters, such as a greater absence of plaque, less clinical signs of gingival inflammation, less probing depth, lower level of clinical insertion and higher level of alveolar bone when compared to those who never undergo this therapy. Conclusion: Thus, statins and bisphosphonates have promising effects in patients under treatment for their respective systemic condition in improving periodontal parameters, but it is important to emphasize that further studies on the subject are needed to better understand the long-term effects of the use of these drugs.(AU)

Dental Follicle Stem Cells Promote Periodontal Regeneration through Periostin-Mediated Macrophage Infiltration and Reprogramming in an Inflammatory Microenvironment.

Dental follicle stem cells (DFSCs) have been verified to promote periodontal regeneration in an inflammatory microenvironment. When coping with inflammatory stimulation, DFSCs highly express periostin, a bioactive molecule closely related to periodontal homeostasis. It is worth exploring whether and how periostin plays a role in the promotion of periodontal regeneration by DFSCs. By tracking the fate of DFSCs, it was found that DFSCs significantly contributed to periodontal regeneration in rat periodontal defects while they had a low survival rate. They highly expressed periostin and improved the immune microenvironment in the defect area, especially via the recruitment and reprogramming of macrophages. Silencing periostin attenuated the effects of DFSCs in promoting periodontal regeneration and regulating macrophages. Recombinant human periostin (rhPeriostin) could not only directly promote macrophage reprogramming through the integrin αM/phosphorylated extracellular signal-regulated kinase (p-Erk)/Erk signaling pathway, but it also exhibited the potential to promote periodontal regeneration in rats when loaded in a collagen matrix. These results indicated that periostin is actively involved in the process by which DFSCs promote periodontal regeneration through the regulation of macrophages and is a promising molecular agent to promote periodontal regeneration. This study provides new insight into the mechanism by which DFSCs promote periodontal regeneration and suggests a new approach for periodontal regeneration therapy.

Improved Healing after Non-Surgical Periodontal Therapy Is Associated with Higher Protein Intake in Patients Who Are Non-Smokers.

The aim of this study was to determine whether a relationship between periodontal healing and protein intake exists in patients undergoing non-surgical treatment for periodontitis. Dietary protein intake was assessed using the 2005 Block food frequency questionnaire in patients with chronic generalized periodontitis undergoing scaling and root planing (n = 63 for non-smokers, n = 22 for smokers). Protein intake was correlated to post-treatment probing depth using multiple linear regression. Non-smoking patients who consumed ≥1 g protein/kg body weight/day had fewer sites with probing depth ≥ 4 mm after scaling and root planing compared to patients with intakes <1 g protein/kg body weight/day (11 ± 2 versus 16 ± 2, p = 0.05). This relationship was strengthened after controlling for baseline probing depth, hygienist and time between treatment and follow-up (10 ± 2 versus 16 ± 1, p = 0.018) and further strengthened after controlling for potential confounders including age, sex, body mass index, flossing frequency, and bleeding on probing (8 ± 2 versus 18 ± 2, p < 0.001). No associations were seen in patients who smoked. Consuming ≥1 g protein/kg body weight/day was associated with reductions in periodontal disease burden following scaling and root planing in patients who were non-smokers. Further studies are needed to differentiate between animal and plant proteins.

The effect of hyaluronic acid on the periodontium in spontaneous periodontitis in rats / El efecto del ácido hialurónico sobre el periodonto en periodontitis espontánea en ratas

SUMMARY: The aim of the article was to study changes in periodontal tissues in rats with spontaneous periodontitis (SP) and to evaluate the effect of hyaluronic acid (HA) on the state of the periodontium. Wistar rats with signs of SP were divided into 6 groups: 1) intact group; 2) intact animals with HA "HD-1,0 MDa"; 3) SP group; 4) SP with HA "S-2,4 MDa"; 5) SP with HA "ST-2,4 MDa"; 6) SP with HA "HD-1,0 MDa". The study of the periodontium rats with SP noted the main structural changes (collagen reduction, resorption of alveolar bone, dilatation and stasis of the vessels of the periodontium, gingival papilla and tooth pulp), which were assessed as moderate. Morphological evidence of inflammation was infiltration of neutrophils into the connective tissue of the gums, without the formation of abscesses. Local administration of HA did not cause additional structural damage in periodontal tissues of rats with SP, but also did not affect changes in the microvascular system of periodontium and tooth pulp, periodontal ligaments, only a tendency to inhibit alveolar bone resorption in rats was noted. One can consider the tendency to improve the condition of periodontal tissues in the group of rats injected with high molecular HA and HA with mannitol (2.4 MDa).

RESUMEN: El objetivo del artículo fue estudiar los cambios en los tejidos periodontales en ratas con periodontitis espontánea (PE) y evaluar el efecto del ácido hialurónico (HA) sobre el estado del periodonto. Las ratas Wistar con signos de PE se dividieron en 6 grupos: 1) grupo intacto; 2) animales intactos con HA "HD-1,0 MDa"; 3) grupo PE; 4) PE con HA "S-2,4 MDa"; 5) PE con HA "ST-2,4 MDa"; 6) PE con HA "HD-1,0 MDa". En las ratas con PS se observaron los principales cambios estructurales (reducción de colágeno, reabsorción del hueso alveolar, dilatación y estasis de los vasos del periodonto, papila gingival y pulpa dentaria), que fueron evaluados como moderados. La evidencia morfológica de inflamación fue la infiltración de neutrófilos en el tejido conectivo de las encías, sin la formación de abscesos. La administración local de HA no causó daño estructural adicional en los tejidos periodontales de las ratas con PE, pero tampoco se produjo cambios en el sistema microvascular del periodonto y en la pulpa dental y ligamentos periodontales.Se observó una tendencia a inhibir la resorción del hueso alveolar. Se puede considerar la tendencia a mejorar el estado de los tejidos periodontales en el grupo de ratas inyectadas con HA de alto peso molecular y HA con manitol (2,4 MDa).

Comparing the sub-gingival levels of Cytomegalovirus, Epstein-Barr virus, Porphyromonas gingivalis in human immunodeficiency virus-1 seropositive patients with and without antiretroviral therapy.

OBJECTIVES: The effect of antiretroviral therapy (ART) on the oral pathogenic microbes in human immunodeficiency virus-1 seropositive patients remains relatively unexplored. Thus, the present study assessed the effect of ART on the sub-gingival levels of 3 pathogenic microbes. MATERIALS AND METHODS: The study groups consisted of 60 human immunodeficiency virus-1 seropositive patients divided into 3 groups of 20 each. Group 1 had periodontitis and did not start with the ART. Group 2 had periodontitis and started with ART (Tenofovir Disoproxil Fumarate 300 mg + Lamivudine 300 mg + Efavirenz 600 mg) at least 6 months before the study. Group 3 with normal periodontium, and have not started ART. The sub-gingival loads of Cytomegalovirus, Epstein-Barr virus, and the Porphyromonas gingivalis levels were assessed, along with the CD4 counts. RESULTS: The cytomegalovirus load was highest in group 1, followed by groups 2, and 3 (p-value of 0.271). The Epstein-Barr load was highest for group 2, followed by group 3, and 1 (p-value of 0.022). The P.gingivalis load was highest in group 2, followed by groups 1 and 3, (p-value of 0.028). The Epstein-Barr and Cytomegalovirus counts were significantly higher (p-value < 0.02) when the CD4 counts were less than 500 cells/cu3. CONCLUSION: ART did not cause any significant reduction in the sub-gingival levels of any of the 3 examined microbes. Given the lack of any significant effect on the sub-gingival microbial loads by the ART, human immunodeficiency virus patients may require additional anti-microbial agents and regular mechanical plaque removal to maintain their periodontal status.

Necrotizing periodontal diseases in human immunodeficiency virus-infected patients receiving highly active antiretroviral therapy: A review.

Human immunodeficiency virus-infected patients have depleted CD4 lymphocyte counts and are susceptible to a plethora of infections of bacterial, viral, and fungal etiology. In addition to a wide range of systemic manifestations, human immunodeficiency virus-infected patients also display several characteristic oral manifestations. Studies have shown a correlation between some of the oral manifestations and CD4 lymphocyte counts which in turn is an independent prognostic indicator. To tackle the human immunodeficiency virus numerous drugs have been discovered and implemented. To overcome any potential resistance, human immunodeficiency virus patients are prescribed highly active antiretroviral therapy, wherein a combination of antiretroviral regimens are used. Studies have shown that in addition to controlling the viral activity, the treatment regimen, has a significant effect on the oral manifestations of the human immunodeficiency virus-infected patients. The present paper highlights the effects of highly active antiretroviral therapy on periodontal diseases in human immunodeficiency virus-infected individuals.

Glucagon-Like Peptide-1 Receptor Agonist Liraglutide Ameliorates the Development of Periodontitis.

Periodontitis is one of the diabetic complications due to its high morbidity and severity in patients with diabetes. The prevention of periodontitis is especially important in diabetic patients because the relationship between diabetes and periodontitis is bidirectional. Here, we evaluated the impacts of glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide on the amelioration of periodontitis. Five-wk-old Male Sprague-Dawley (SD) rats (n = 30) were divided into 3 groups: normal, periodontitis, and periodontitis with liraglutide treatment groups. Periodontitis was induced by ligature around the maxillary second molar in SD rats. Half of the rats were administered liraglutide for 2 weeks. Periodontitis was evaluated by histological staining, gene expressions of inflammatory cytokines in gingiva, and microcomputed tomography. Periodontitis increased inflammatory cell infiltration, macrophage accumulation, and gene expressions of tumor necrosis factor-α and inducible nitric oxide synthase in the gingiva, all of which were ameliorated by liraglutide. Liraglutide decreased M1 macrophages but did not affect M2 macrophages in periodontitis. Moreover, ligature-induced alveolar bone resorption was ameliorated by liraglutide. Liraglutide treatment also reduced osteoclasts on the alveolar bone surface. These results highlight the beyond glucose-lowering effects of liraglutide on the treatment of periodontitis.

Sclerostin antibody stimulates periodontal regeneration in large alveolar bone defects.

Destruction of the alveolar bone in the jaws can occur due to periodontitis, trauma or following tumor resection. Common reconstructive therapy can include the use of bone grafts with limited predictability and efficacy. Romosozumab, approved by the FDA in 2019, is a humanized sclerostin-neutralizing antibody (Scl-Ab) indicated in postmenopausal women with osteoporosis at high risk for fracture. Preclinical models show that Scl-Ab administration preserves bone volume during periodontal disease, repairs bone defects surrounding dental implants, and reverses alveolar bone loss following extraction socket remodeling. To date, there are no studies evaluating Scl-Ab to repair osseous defects around teeth or to identify the efficacy of locally-delivered Scl-Ab for targeted drug delivery. In this investigation, the use of systemically-delivered versus low dose locally-delivered Scl-Ab via poly(lactic-co-glycolic) acid (PLGA) microspheres (MSs) was compared at experimentally-created alveolar bone defects in rats. Systemic Scl-Ab administration improved bone regeneration and tended to increase cementogenesis measured by histology and microcomputed tomography, while Scl-Ab delivered by MSs did not result in enhancements in bone or cemental repair compared to MSs alone or control. In conclusion, systemic administration of Scl-Ab promotes bone and cemental regeneration while local, low dose delivery did not heal periodontal osseous defects in this study.

Investigation of the Effect of Formaldehyde on the Condition of Periodontal Tissues of Woodworking Industry Workers.

The high prevalence of periodontal diseases in workers with professional contact with unfavorable factors of the production environment is an unresolved problem of dentistry. This study aimed to investigate the harmful effects of formaldehyde on periodontal tissues in woodworkers who have long-term contact with formaldehyde in their professional activities. Sixty-nine men with occupational exposure to formaldehyde were examined to study the effect of formaldehyde on the human periodontal tissues, looking particularly at signs of the periodontal tissues' inflammatory process using a series of periodontal indices. The study results showed that the condition of periodontal tissues was statistically significantly worse in woodworkers who have long-term contact with formaldehyde in their professional activities. However, the hygiene status was not significantly different in the main group and the comparison group. Thus, we concluded that working under conditions of constant exposure to formaldehyde has a negative effect on the condition of periodontal tissues.

Current Evidence of Natural Agents in Oral and Periodontal Health.

Oral and periodontal diseases, chewing disorders, and many destructive inflammatory diseases of the supporting tissues of the teeth are usually caused by an imbalance between host defense and environmental factors like smoking, poor nutrition, and a high percentage of periodontopathogenic bacteria. For these reasons, it is important also to focus attention on plaque control and also on improving host resistance through smoking and stress reduction, and a healthy diet. During the last decades, the importance of micronutrients has been extensively reviewed, and it was concluded that the prevention and treatment of periodontitis should include correct daily nutrition and a correct balance between antioxidants, probiotics, natural agents, vitamin D, and calcium. Recently, there has been growing interest in the literature on the impact of nutraceutical dietary aliments on oral and general health. This Special Issue provides a current and thoughtful perspective on the relationship of diet and natural agents on oral and periodontal diseases through a correct clinical approach with the last and most important evidence that may determine good oral conditions and high quality of life.

Response of inflammatory cells to biodegradable ultra-fine grained Mg-based composites.

Ultra-fine grained biodegradable Mg-based Mg1Zn1Mn0.3 Zr - HA and Mg4Y5.5Dy0.5 Zr - 45S5 Bioglass composites have shown great medical potential. Two types of these Mg-based biomaterials subjected to different treatments were tested and as shown earlier they are biocompatible. The aim of the study is to determine how much culture media incubated with these ultra-fine trained Mg-based composites can cause inflammatory reactions and /or periodontal cell death. The incubation of composites in the medium releases metal ions into the solution. It can be assumed that this process is permanent and also occurs in the human body. The results have shown that the effect of proinflammatory IL-6 and TNF- cytokines results in the strongest production of the acute phase proteins in the first day on the Mg1Zn1Mn0.3 Zr-5 wt.% HA-1 wt. % Ag HF-treated biocomposite after immersion for 2 h in 40 % HF and then the fastest decrease in these processes on the third day. In turn, the inflammatory process induced on the Mg1Zn1Mn0.3 Zr-5 wt.% HA-1 wt. % Ag biomaterial, in BAX / BCL ratio assessment, is the strongest on the third day and maintains a significantly high level on the following day, which, at the same time, confirms its persistence and development. In addition, these results confirm the successively generated necrotic processes. Ions can induce inflammatory reactions, which in the case of the implant may take a long time, which results in the loss of the implant. Even if the material is biocompatible in rapid in-vitro tests, it can induce inflammation in the body after some time due to the release of ions. Not every treatment improves the material's properties in terms of subsequent safety.

Sustained Release of Two Bioactive Factors from Supramolecular Hydrogel Promotes Periodontal Bone Regeneration.

Intact and stable bone reconstruction is ideal for the treatment of periodontal bone destruction but remains challenging. In research, biomaterials are used to encapsulate stem cells or bioactive factors for periodontal bone regeneration, but, to the best of our knowledge, using a supramolecular hydrogel to encapsulate bioactive factors for their sustained release in bone defect areas to promote periodontal bone regeneration has not been reported. Herein, we used a well-studied hydrogelator, NapFFY, to coassemble with SDF-1 and BMP-2 to prepare a supramolecular hydrogel, SDF-1/BMP-2/NapFFY. In vitro and in vivo results indicated that these two bioactive factors were ideally, synchronously, and continuously released from the hydrogel to effectively promote the regeneration and reconstruction of periodontal bone tissues. Specifically, after the bone defect areas were treated with our SDF-1/BMP-2/NapFFY hydrogel for 8 weeks using maxillary critical-sized periodontal bone defect model rats, a superior bone regeneration rate of 56.7% bone volume fraction was achieved in these rats. We anticipate that our SDF-1/BMP-2/NapFFY hydrogel could replace bone transplantation in the clinic for the repair of periodontal bone defects and periodontally accelerated osteogenic orthodontics in the near future.

Sclerostin injection enhances orthodontic tooth movement in rats.

OBJECTIVE: It was aimed to investigate the in vivo effects of local injection of sclerostin protein on orthodontic tooth movement. DESIGN: A total of 48 rats underwent orthodontic mesialization of the maxillary first molars on both sides. Local injection was given at the compression side in the alveolar bone on both maxillary sides, with sclerostin protein carried by hydrogel on one side, and the same volume of normal saline carried by hydrogel on the other side serving as the control. After two weeks, the tooth movement amount and effects on the periodontium were assessed through micro-computed tomography (µCT) analysis, tartrate-resistant acid phosphatase (TRAP) staining and immunohistochemistry (IHC) analysis. RESULTS: After two weeks of intervention, tooth movement was significantly greater in the 4 µg/kg and 20 µg/kg sclerostin injection groups, compared to the control. Analysis of the furcation area of the maxillary first molar showed that the 20 µg/kg group had significantly decreased BV/TV. At the compression side, the number of TRAP-positive osteoclasts was significantly increased in 20 µg/kg group compared to the control. The expression of RANKL was statistically higher in all the sclerostin groups, while the expression of OPG was statistically lower in the 4 µg/kg and 20 µg/kg groups, compared to the control. At the tension side, the expression of RUNX2 and COL-1 was statistically higher in the 20 µg/kg group compared to the control. CONCLUSIONS: Local injection of sclerostin protein in the alveolar bone at the compression side accelerates OTM in rats by promoting osteoclastogenesis.

Effects of formaldehyde on vascular endothelial growth factor, matrix metallopeptidase 2 and osteonectin levels in periodontal membrane and alveolar bone in rats.

BACKGROUND: The objective of this study was to investigate whether long term formaldehyde inhalation may affect periodontal membrane and alveolar bone loss leading to periodontitis. The negative effects of formaldehyde were described using vascular endothelial growth factor (VEGF), matrix metallopeptidase 2 (MMP-2) and osteonectin antibodies involved in the extracellular matrix and angiogenetic development. MATERIALS AND METHODS: Thirty adult Wistar albino rats were used in this study. Rats were divided into two groups: a control group (n = 15) and formaldehyde administered group (n = 15). Formaldehyde group was exposed to inhalation of 10 ppm formaldehyde 8 hours a day, 5 days a week for 5 weeks. Maxillary bone regions were dissected under anaesthesia. After fixation in 10% formaldehyde solution, tissues were passed through graded ethanol series to obtain paraffin blocks. Five-micrometre histological sections were cut with RM2265 rotary microtome stained with Masson trichrome and VEGF, MMP-2 and osteonectin antibodies for examination under Olympus BH-2 light microscopy. RESULTS: The present study revealed that congestion in blood vessels, degeneration of collagen fibres and alveolar matrix around alveolar bone were observed to be more significant in formaldehyde group than the control group (p ≤ 0.001). Interestingly, VEGF expression in the formaldehyde group was the most significant finding between the two groups (p < 0.001). When compared inflammation, MMP-2 and osteonectin expressions were significant (p < 0.01) in the formaldehyde group. CONCLUSIONS: It was suggested that formaldehyde toxicity decreased the expression of MMP-2 and in osteoblasts as well as affecting the retention of MMP levels in tooth cavity, which is very low in collagen fibres. But, vice versa for the expression of VEGF in dilated vascular endothelial cells and osteocytes in alveolar bone. As a conclusion, formaldehyde disrupts the periodontal membrane and may cause collagen fibres degeneration by affecting the alveolar bone matrix.

Periodontal complications of prescription and recreational drugs.

Drug use for both therapeutic and recreational purposes is very widespread in most societies. The range of drugs used, the variations in response to these drugs and other health and behavioral confounders mean that drug use may be an important contributor to individualized periodontal diagnoses. In this narrative review, we review the main reported effects of drugs on the periodontal tissues and periodontal disease processes. Although some of the more common adverse drug reactions on periodontal tissues are well described, in many other cases the evidence for these drug effects is quite limited and based on small case series or isolated reports. Prescription drugs are responsible for a range of effects, including drug-induced gingival overgrowth and increased gingival bleeding, and influence periodontal inflammation and periodontal breakdown. The effects of recreational drugs on the periodontal tissues is less well researched, perhaps for the obvious reason that assembling large cohorts of recreational drug users presents particular challenges. Use of nearly all of these substances is associated with poorer periodontal and dental health, although there is almost certainly a large degree of behavioral confounding in these findings. Overall, further studies of adverse drug reactions on the periodontal tissues are required as this continues to be an important and increasing factor in periodontal health determination.

Fibrillin-1 insufficiency alters periodontal wound healing failure in a mouse model of Marfan syndrome.

OBJECTIVE: Marfan syndrome (MFS) is a systemic connective tissue disorder caused by insufficient fibrillin-1 (FBN-1), a major component of microfibrils that controls the elasticity and integrity of connective tissues. FBN-1 insufficiency in MFS leads to structural weakness, which causes various tissue disorders, including cardiovascular and periodontal disease. However, the role of FBN-1 insufficiency in the destruction and regeneration of connective tissue has not yet been clarified. To investigate the role of FBN-1 insufficiency in tissue destruction and regeneration. DESIGN: We used a ligature-induced (LI) periodontal disease model in fbn-1-deficient mice (fbn-1c1039G/+ mice) with MFS and investigated the regeneration level of periodontal tissue and as an inflamatic marker, the expression of the matrix metalloproteinase (mmp)-9 and tumor necrosis factor (tnf)-α. RESULTS: Interestingly, fbn-1c1039G/+ mice exhibited slowed wound healing compared with wild type mice, but periodontal tissue destruction did not differ between these mice. Moreover, fbn-1c1039G/+ mice exhibited delayed bone healing in association with continuous mmp-9 and tnf-α expression. Furthermore, inflammatory cells were obvious even after the removal of ligatures. CONCLUSION: These data suggest that fibrillin-1 insufficiency in fbn-1c1039G/+ mice interfered with wound healing in connective tissue damaged by inflammatory diseases such as periodontal disease.

Ipriflavone promotes proliferation and osteogenic differentiation of periodontal ligament cells by activating GPR30/PI3K/AKT signaling pathway.

OBJECTIVES: This study was performed to investigate the effects and mechanism of ipriflavone (IP) on the proliferation and osteoblastic differentiation of periodontal ligament cells in vitro and periodontal tissue remodeling following orthodontic tooth movement (OTM) in vivo. MATERIALS AND METHODS: Human periodontal ligament cells (hPDLCs) were cultured in vitro and cell counting kit-8, alkaline phosphatase (ALP) activity assay, plate clone formation assay, and alizarin red staining were used to test proliferation and osteogenic differentiation of hPDLCs. What is more, the expression of ALP, Runx2, and GPR30 was examined by real-time polymerase chain reaction and Western blot. To find out if PI3K/AKT signaling pathway was involved in the process, AKT and p-AKT were examined by Western blot. LY294002 (PI3K signaling pathway inhibitor) and small interfering RNA targeting GPR30 mRNA (siGPR30) were used to verify the function of GPR30-mediated PI3K/AKT pathway in this process. Twenty-four male Wistar rats were randomized into 2 groups, the control group with force application and the IP group with force application plus IP. Morphological changes in the periodontal tissue between roots of teeth were investigated using hematoxylin and eosin (HE) staining and bone morphogenetic protein-2 was detected to assess bone remodeling by immunohistochemical staining. RESULTS: In vitro, 10-7 M IP was selected significantly promoting proliferation, ALP activity, colony forming efficiency, and mineral deposition (P<0.05) on hPDLCs. Gene expressions of ALP, Runx2, GPR30, and p-AKT were all upregulated than the control group (P<0.05). According to the mechanism, promotion of ALP and Runx2 interdicted by LY294002 and siGPR30 reduced the activation of PI3K/AKT signaling pathway. In addition, HE staining and immunohistochemical staining results showed that the IP group had more new bone formation in the periodontal tissue compared to the control group in vivo. CONCLUSION: IP can promote the expression of ALP and Runx2 which was probably related to the GPR30-mediated PI3K/AKT signaling pathway. Moreover, IP coordination seemed to have the potential to prevent relapsing following OTM.

Local administration of Tiludronic Acid downregulates important mediators involved in periodontal tissue destruction in experimental periodontitis in rats.

OBJECTIVE: The purpose of this study was to evaluate whether local administration of TIL could influence the expression of the inflammatory mediators IL-1ß, TNF-α, MMP-8 and COX-2 in rats with experimental periodontitis (EP). METHODS: Twenty-four adult male rats (Rattus norvegicus, albinus, Wistar) were assigned to groups C, EP, EP-TIL (CControl group, EP-Periodontitis groups). On EP groups, a ligature was placed around maxillary 2nd molars on day 1. On group EP-TIL, 20 µL of TIL solution (1 mg/kg body weight) was injected into the subperiosteal palatal area adjacent to the maxillary 2nd molar every other day until euthanasia (day 11). Alveolar bone loss was morphometrically analyzed. mRNA expressions of IL-1ß, TNF-α, MMP-8 and COX-2 were assessed by qPCR. IL-1ß, TNF-α, MMP-8 and COX-2 were immunohistochemically analyzed. Data were analyzed statistically. RESULTS: Group EP-TIL presented reduced alveolar bone loss when compared with group EP (p < 0.05). Group EP-TIL presented decreased mRNA expressions of IL-1ß, TNF-α, MMP-8 and COX-2 and reduced immunolabeling of IL-1ß, TNF-α and MMP-8 when compared with group EP (p < 0.05). No differences regarding the immunolabeling of COX-2 were found when group EP-TIL was compared with the other groups (p > 0.05). CONCLUSION: Within the limits of this study, it can be concluded that local administration of TIL downregulates important mediators involved in periodontal tissue destruction in ligature-induced periodontitis in rats.

Khat (Catha edulis) and its oral health effects: An updated review.

Khat or qat (Catha edulis) is a plant that grows in East Africa and southern Arabia. The leaves and twigs of this small tree are chewed by several millions of people worldwide for their stimulating amphetamine-like effects. The reported prevalence of khat chewing in Europe and the USA is on the rise, especially with global migration. Long-term khat chewing has several detrimental general and oral health effects. The aim of the present study was to review the current literature regarding khat use and its association with oral and dental diseases, with particular emphasis on its link with oral keratotic white lesions and oral cancer. We searched the literature to identify all relevant articles. Studies showed that khat is associated with several oral and dental conditions, including keratotic white lesions, mucosal pigmentation, periodontal disease, tooth loss, plasma cell stomatitis, and xerostomia. There are limited data on the incidence of dental caries among khat chewers. The evidence that khat chewing is a risk factor for oral cancer is still weak, and is mainly based on anecdotal case reports and uncontrolled studies.

Chitosan-triclosan particles modulate inflammatory signaling in gingival fibroblasts.

BACKGROUND AND OBJECTIVES: An important goal of periodontal therapy is the modulation of the inflammatory response. To this end, several pharmacological agents have been evaluated. Triclosan corresponds to an antibacterial and anti-inflammatory agent currently used in periodontal therapy. Chitosan is a natural polymer that may act as a drug delivery agent and exerts antibacterial and anti-inflammatory activities. Therefore, an association between both molecules might be useful to prevent inflammation and tissue destruction in periodontal tissues. MATERIAL AND METHODS: In the present study, we have generated chitosan-triclosan particles and evaluated their morphology, charge, biocompatibility and gene expression analysis in human gingival fibroblasts. RESULTS: The chitosan-triclosan particles size and Z potential were 129 ± 47 nm and 51 ± 17 mV respectively. Human gingival fibroblast viability was not affected by chitosan-triclosan. A total of 1533 genes were upregulated by interleukin (IL)-1ß. On the other hand, 943 were downregulated in fibroblasts stimulated with IL-1ß plus chitosan-triclosan particles. Fifty-one genes were identified as molecular targets upregulated by IL-1 ß and downregulated by the chitosan-triclosan particles. The gene ontology analysis revealed that these genes were enriched in categories related to biological processes, molecular function and cellular components. Furthermore, using real-time reverse transcription-polymerase chain reaction beta-actin, fibronectin, interleukin-6 and IL-1b genes were confirmed as targets upregulated by IL-1ß and downregulated by chitosan-triclosan particles. CONCLUSION: Our results show that chitosan-triclosan particles are able to modulate the inflammatory response in gingival fibroblasts. This effect might be useful in the prevention and/or treatment of inflammation in periodontal diseases.