Role of the gene Slc11a1 and selected genotypes for minimum and maximum inflammatory reactivity in the process of alveolar bone healing in mice / Papel do gene Slc11a1 e de genótipos selecionados para mínima e máxima reatividade inflamatória no processo de reparo ósseo alveolar em camundongos

The process of alveolar bone healing can be influenced by several local and systemic factors, which include the immune system and healing related genes. However, the exact role of host inflammatory responsiveness and genetic background in bone healing process remains unclear. In this context, we evaluated the influence inflammation in alveolar bone healing taking advantage of mice strains genetically selected for maximum (AIRmax) or minimum (AIRmin) acute inflammatory response, as well AIR strains homozygous for RR/SS Slc11a1 genotypes. Experimental groups (N=5/time/group) comprised 8-week-old male or female AIRmax and AIRmin; and substrains AIRminRR, AIRminSS and AIRmaxRR and AIRmaxSS; submitted to extraction of upper right incisor and evaluated at 0, 3, 7, 14 and 21 days after upper incision extraction by micro-computed tomography (CT), histomorphometry, birefringence, immunohistochemistry and molecular (PCRArray) analysis. Initially, our results demonstrated that AIRmin mice presented an early increase (p<0.05) in bone volume, hyperdense regions, density of bone matrix and osteoblasts, increased (p<0.05) expressed of BMP4, BMP7 and RUNX2 when compared to AIRmax strain. AIRmin mice also presented lower counts of GR1+ and CD80+ cells, and higher counts of F4/80+ and CD206+ cells, in parallel with higher mRNA expression of CX3CL1, CCL5, CCR5 and ARG when compared to AIRmax animals. In late repair stages, the AIRmin strain presented a decreased (p<0.05) density of osteoclast and blood vessels than AIRmax, along lower RANKL and Catepk and higher PHEX and SOST mRNA expression, but the healing outcome at the endpoint was similar in AIRmin and AIRmax strains. When analyzed the effect of RR/SS Slc11a1 genotypes was evaluated in parallel with the influence AIRmin/AIRmax background, we initially observed that the AIRmax strain, associated with both RR and SS Slc11a1 genotypes, presented a more effective bone healing, characterized by increased (p<0.05) of bone volume and predominance of red fiber in analysis in contrast to AIRmin strains. AIRmaxRR presented increased (p<0.05) F4/80+ and decreased CD80+ e CD206+ cells count, while AIRmaxSS presented increased (p<0.05) GR1+, F4/80+ and CD80+ and decreased CD206+ cells. When the analysis was performed in order to address the influence Slc11a1 variants, AIRmaxSS strain presented a bone healing delay when compared to AIRmaxRR; characterized by decreased (p<0.05) of bone volume, trabecular number and red collagen fibers, increased (p<0.05) GR1+ and CD80+ and decreased F4/80+ and CD206+. Conversely, AIRminSS presented a more effective healing when compared with AIRminRR mice; characterized by increased (p<0.05) of bone volume, trabecular number/separation and red birefringence, increased GR1+ and decreased CD206+ cells count. In conclusion, while AIRmin and AIRmax strains presents a similar healing outcome at the endpoint, the early repair in AIRmin strain was associated with decreased presence of neutrophils and M1 macrophages, and increased M2 macrophages. Additionally, our while results showed that AIRmax inflammatory background was associated to a more effective bone healing process irrespective of the presence of RR/SS Slc11a1 genotypes, RR genotype favors the healing in AIRmax background and SS genotype was found to favor the healing in the AIRmin background.(AU)

O processo de reparo ósseo alveolar pode ser influenciado por vários fatores locais e sistêmicos, que incluem o sistema imunológico e os genes relacionados ao reparo. No entanto, o exato papel da resposta inflamatória do hospedeiro e genético background no processo de reparo ósseo ainda não está claro. Neste contexto, avaliamos a influência da inflamação no reparo óssea alveolar, em camundongos selecionadas geneticamente para uma resposta inflamatória aguda máxima (AIRmax) ou mínima (AIRmin), como também em camundongos AIR homozigoto para os alelos RR/SS do gene Slc11a1.Neste estudo foram utilizados camundongos machos e fêmeas (N=5/tempo/grupo), das linhagens selecionados para máxima e mínima (AIRmax e AIRmin) reação inflamatória, e também as sublinhagens AIRminRR, AIRminSS, AIRmaxRR e AIRmaxSS com idade aproximada de 8 semanas. Todos foram submetidos à extração do incisivo superior direito e avaliados nos períodos de 0, 3, 7, 14 e 21 dias pós extração, seguido pela análise tomografia computadorizada (CT), análise histomorfometria, análise de birrefringência, análise imuno-histoquímica e análise molecular (PCRArray). Inicialmente, nossos resultados demonstraram que a linhagem AIRmin, no período inicial, apresentou um aumento (p<0.05) no volume ósseo, nas regiões hiperdensas, na densidade de matriz óssea e osteoblastos, seguido pelo aumento (p<0.05) na expressão de BMP4, BMP7 e RUNX2 quando comparado a linhagem AIRmax. Camundongos AIRmin também apresentou uma menor contagem de células GR1+ e CD80+ e aumento da contagem de células F4/80+ e CD206+, em paralelo com aumento da expressão de mRNA de CX3CL1, CCL5, CCR5 e ARG quando comparado aos camundongos AIRmax. Nos períodos tardios, a linhagem AIRmin apresentou uma diminuição (p<0.05) na densidade de osteoclastos e vasos sanguíneos em comparação AIRmax, seguido por uma diminuição na expressão de mRNA de RANKL e Catepk e aumento de PHEX e SOST, mas o processo de reparo ósseo alveolar, no período final foi semelhante entres as linhagens AIRmin e AIRmax. Quando analisamos o efeito dos alelos RR/SS do gene Slc11a1 em paralelo com a influência do background AIRmin/AIRmax, nós inicialmente observamos que a linhagem AIRmax associada com ambos os alelos RR/SS do gene Slc11a1 apresentaram um processo de reparo mais efetivo, caracterizado pelo aumento (p<0.05) volume ósseo e predominância de fibras vermelhas em comparação com a linhagem AIRmin. Camundongos AIRmaxRR apresentaram aumento (p<0.05) na contagem de células F4/80+ e diminuição na contagem de células CD80+ e CD206+, enquanto, camundongos AIRmaxSS apresentou um aumento (p<0.05) na contagem de células GR1+, F4/80+, CD80+ e diminuição na contagem de células CD206+. Quando analisamos a influência dos alelos do gene Slc11a1, a linhagem AIRmaxSS apresentaram um atraso no reparo óssea quando comparado ao AIRmaxRR; caracterizado pela diminuição (p<0.05) do volume ósseo, número trabecular e fibras colágenas vermelhas, seguido pelo aumento (p<0.05) da contagem de células GR1+ e CD80+ e diminuição de células F4/80+ e CD206+. Por outro lado, camundongos AIRminSS apresentaram um reparo ósseo mais efetivo quando comparada com AIRminRR; caracterizada pelo aumento (p<0.05) do volume ósseo, número / separação trabecular e birrefringência das fibras colágenas no espectro vermelho, seguido pelo aumento da contagem de células GR1+ e diminuição das células CD206+. Diante disso, os nossos resultados demonstraram que as linhagens AIRmin e AIRmax apresentaram um processo de reparo ósseo alveolar semelhantes no período final do reparo, enquanto no reparo inicial a linhagem AIRmin estava associada com a diminuição de neutrófilos e macrófagos M1 e aumento dos macrófagos M2. Além disso, nossos resultados demonstraram que background AIRmax estava associado a um processo de reparo mais efetivo, independentemente da presença de genótipos RR/SS Slc11a1, o genótipo RR favorece o reparo no background AIRmax e o genótipo SS favoreceu a reparo no background AIRmin.(AU)

Maxillomandibular giant osteosclerotic lesions

Abstract Giant Osteosclerotic Lesions (GOLs) are a group of rarely reported intraosseous lesions. Their precise diagnosis is important since they can be confused with malignant neoplasms. Objective This retrospective study aimed to record and analyze the clinical and radiographic Giant Osteosclerotic Lesions (GOLs) detected in the maxillomandibular area of patients attending to our institution. Materials and Methods: Informed consent from the patients was obtained and those cases of 2.5 cm or larger lesions with radiopaque or mixed (radiolucid-radiopaque) appearance located in the maxillofacial bones were selected. Assessed parameters were: age, gender, radiographic aspect, shape, borders, size, location and relations to roots. Lesions were classified as radicular, apical, interradicular, interradicular-apical, radicular-apical or located in a previous teeth extraction area. Additionally, several osseous and dental developmental alterations (DDAs) were assessed. Results Seventeen radiopacities in 14 patients were found and were located almost exclusively in mandible and were two types: idiopathic osteosclerosis and condensing osteitis. GOLs were more frequent in females, and in the anterior and premolar zones. 94.2% of GOLs were qualified as idiopathic osteosclerosis and one case was condensing osteitis. All studied cases showed different osseous and dental developmental alterations (DDAs). The most common were: Microdontia, hypodontia, pulp stones, macrodontia and variations in the mental foramina. Conclusions GOLs must be differentiated from other radiopaque benign and malignant tumors. Condensing osteitis, was considered an anomalous osseous response induced by a chronic low-grade inflammatory stimulus. For development of idiopathic osteosclerosis, two possible mechanisms could be related. The first is modification of the normal turnover with excessive osseous deposition. The second mechanism will prevent the normal bone resorption, arresting the osseous breakdown process.

Tratamiento de la osteítis condensante en molar: informe de caso / Molar condensing osteitis treatment: Case report

En la actualidad, la principal causa por la que acuden los pacientes al odontólogo es el dolor dental, endonde la mayoría presenta un padecimiento pulpar o periapical irreversibles, que pueden estar asociados a factores traumáticos e irritativos. Sin embargo, pocosde ellos son asintomáticos, como la osteítis condensante que es escasamente mencionada en elámbito de la Endodoncia; por lo tanto, el objetivo de este caso clínico es el de proporcionar información acerca de la osteítis condensante siguiendo los lineamientos internacionales de Case Report (CARE). La osteítis condensante tiene una incidencia muy baja en pacientes y se debe diagnosticar correctamente al momento de tratar este tipo de lesiones con las diferentes herramientas de diagnóstico que se conocen. En este caso, se presenta un paciente del sexo femenino de 58 años de edad con un estado prediabético, que refiere un fractura del segundo molar inferior derecho, al cual radiográficamente se le encontróuna lesión periapical radiopaca en la raíz distal. Se muestra la secuencia del tratamiento, el manejo clínico y la rehabilitación.

At present, the main reason for patients to visit adentist is dental pain, where most of them presenta pulp or periapical irreversible condition, whichmay be associated with traumatic and irritative factors. However, few of them are asymptomatic as osteitiscondensing that is barely mentioned in thefield of endodontics. The aim of this case report isto provide information about the condensing osteitisfollowing international Case Report (CARE)guidelines. Condensing osteitis has a very low incidence in patients and should be correctly diagnosed with the different available diagnostic tools. In thiscase a 58-years-old female patient, with prediabeticstate, referred of a right lower second molar fracturewhich radiographically showed a radiopaque periapicallesion in the distal root of the molar. The sequence of treatment, clinical management and rehabilitation is presented.

Medication-related osteonecrosis of the jaw. Introduction of a new modified experimental model

ABSTRACT PURPOSE : To evaluate a modified experimental model for medication-related osteonecrosis of the jaw (MRONJ) through the upper right central incisor extraction followed by intravenous bisphosphonate administration. METHODS: Forty five rats underwent the upper right central incisor tooth extraction were divided in 2 groups: Group I - experimental group, 30 rats received an intravenous administration protocol of zoledronic acid 35μg/kg into the tail vein every two weeks, totalizing four administrations, during eight weeks of administration, previously the extraction, and Group II - control group, 15 rats didn't received any medication before extraction. The groups were subdivided in postoperative periods: 14/28/42 days. Clinical analysis and microtomography were performed to verify the presence of osteonecrosis. In addition, descritive histological analysis of hematoxylin-eosin stained sections was performed to evaluate the presence of osteonecrosis or necrotic foci. RESULTS: Twelve (40%) rats, from experimental group, showed clinical signs of MRONJ (p=0.005), however, all samples showed imaginologic findings like osteolysis and loss of integrity of the cellular walls (p≤0.001). Microscopic evaluation revealed osteonecrosis areas with microbial colonies and inflammatory infiltrate (p≤0.001). In the control group, all animals presented the chronology of a normal wound healing. CONCLUSIONS: The presence of medication-related osteonecrosis of the jaw after maxillary central incisor extraction in rats. This new experimental model may be considered an option for the study of MRONJ.

Improvement of bone repair in diabetic rats subjected to ƛ780 nm low-level laser therapy

PURPOSE: To investigate the effect of low-level laser therapy on bone healing in diabetic rats.METHODS: Bone cavities (19 mm diameter) were performed in the femur of 72 alloxan-induced diabetic rats, which were assigned into four groups: CTR (non-diabetic control), DBT (diabetic) CTRL (non-diabetic irradiated) and DBTL (diabetic irradiated). Low-level laser therapy was performed every 48h for seven days. Animals were euthanized at seven, 18 and 30 days. Alkaline phosphatase serum levels and bone repair were analyzed.RESULTS: Low-level laser therapy significantly increased alkaline phosphatase in at seven and 18 days (p<0.001), and improved bone healing at seven (p<0.01), 18 (p<0.05) and 30 (p<0.01) in diabetic animals. In addition, bone healing in irradiated diabetic group was statistically similar to control group at 30 days (p>0.05).CONCLUSION:Low-level laser therapy increased the serum levels of alkaline phosphatase and improved bone healing in alloxan-induced diabetic rats.

Osteitis and mucosal inflammation in a rabbit model of sinusitis / Osteíte e inflamação mucosa em um modelo experimental de rinossinusite

INTRODUCTION: Several experimental studies have shown osteitis after the onset of sinusitis, supporting the idea that bone involvement could participate in the dissemination and perpetuation of this inflammatory disease. However, procedures commonly performed for the induction of sinusitis, such as antrostomies, can trigger sinusitis by themselves. OBJECTIVE: To evaluate osteitis in an animal model of sinusitis that does not violate the sinus directly and verify whether this is limited to the induction side, or if it affects the contralateral side. METHODS: Experimental study in which sinusitis was produced by inserting an obstructing sponge into the nasal cavity of 20 rabbits. After defined intervals, the animals were euthanized and maxillary sinus samples were removed for semi-quantitative histological analysis of mucosa and bone. RESULTS: Signs of bone and mucosal inflammation were observed, affecting both the induction and contralateral sides. Statistical analysis showed correlation between the intensity of osteitis on both sides, but not between mucosal and bone inflammation on the same side, supporting the theory that inflammation can spread through bone structures, regardless of mucosal inflammation. CONCLUSION: This study demonstrated that in an animal model of sinusitis that does not disturb the sinus directly osteitis occurs in the affected sinus and that it also affects the contralateral side. .

INTRODUÇÃO: Diversos estudos experimentais evidenciam osteíte após estabelecimento de sinusite, corroborando para a ideia de que o envolvimento ósseo poderia participar na disseminação e perpetuação do processo inflamatório. Porém procedimentos realizados para indução da doença nestes modelos, como antrostomias, podem, por si só, desencadear osteíte. OBJETIVO: Avaliar osteíte em um modelo de rinossinusite em que não ocorre manipulação sinusal e verificar se esta é limitada ao lado de indução, ou se acomete o lado contralateral. MÉTODO: Estudo experimental em que induziu-se rinossinusite em 20 coelhos, por meio de obliteração temporária com esponja de uma das cavidades nasais. Amostras de tecido sinusal foram submetidas à análise histológica semiquantitativa, após sacrifício dos animais em intervalos regulares. RESULTADOS: Foram observados sinais de inflamação óssea e mucosa mais intensa no lado de indução, mas também contralateral. Testes estatísticos evidenciaram correlação entre a osteíte de ambos os lados, porém não entre inflamação óssea e mucosa de um mesmo lado, apoiando a teoria de que a inflamação poderia se disseminar através do tecido ósseo, independente da inflamação mucosa. CONCLUSÃO: O presente estudo evidenciou a existência de osteíte, tanto no lado de indução quanto no contralateral, em modelo experimental em que não ocorre manipulação sinusal. .

Histomorphometric analysis of bone tissue repair in rabbits after insertion of titanium screws under different torque / Estudo histomorfométrico do reparo tecidual ósseo de coelhos com parafusos de titânio inseridos sob diferentes intensidades de torques

PURPOSE: To evaluate the inflammatory response of rabbit bone after insertion of titanium screws under different torque values. METHODS: Four holes were made in the back tibia of fifteen New Zealand male albino rabbits; three screws were placed in each animal and a control hole remained without a screw. The screws were inserted with 0, 5 or 10 N.cm of torque. The animals were assigned to five groups according to the day of sacrifice after surgery (2, 7, 14, 21 or 42 days). The inflammatory cells and the thickness of the bone tissue around the screws was count. RESULTS: The screws were associated with a larger number of inflammatory cells when compared to the control hole. There was no statistically significant difference when several comparisons were made among the groups with different torque intensity. CONCLUSIONS: The histological changes were not statistically significant. There was a trend toward an increase in inflammatory cells found in local bone tissue surrounding the titanium screws installed with the highest torque. There was a tendency toward the formation of a lower thickness of tissue surrounding those bone screws that were inserted with higher torque.

OBJETIVO: Avaliar em variados períodos de tempo a resposta inflamatória do tecido ósseo de coelhos nos quais foram instalados parafusos de titânio com variadas intensidades de torque. MÉTODOS: 15 coelhos Nova Zelândia receberam três parafusos de titânio instalados em cada tíbia traseira e uma perfuração sem parafuso. Foram inseridos os parafusos com 0, 5 e 10 N.cm de torque. A eutanásia ocorreu 2, 7, 14, 21 e 42 dias pós-operatórios e foram analisados a em microscopia óptica a quantidade de células inflamatórias e espessura do tecido ósseo formado. RESULTADOS: Observou-se que a presença de parafusos apresentou uma quantidade significantemente maior de células inflamatórias quando comparado às perfurações controle. Houve um aumento na formação de tecido ósseo adjacente aos parafusos dos grupos 14, 21 e 42 dias quando comparados aos demais. CONCLUSÕES: Quanto maiores foram os torques de instalação dos parafusos de titânio, maiores foram as quantidades de células inflamatórias locais observadas nos tecidos ósseos circundantes e que com o passar dos períodos de tempo, foram diminuindo gradativamente. As espessuras de tecidos ósseos formadas observadas ao redor dos parafusos inseridos foram proporcionalmente menores quando a intensidade dos torques aplicados foram cada vez maiores.

Plasminogen, fibrinogen and bradykinins in alveolar osteitis in patients receiving oral contraceptives

Two hundred females were examined for the incidence of alveolar osteitis [dry socket], after simple extraction of a mandibular molar. The control group [100 Patients] included 12% positive cases at the middle of their menstrual cycle. In the contraceptive pill users group, the incidence of alveolar osteitis was 36% at the middle of the tablet cycle No cases were reported during menstruation in both groups. The highest levels of plasma plasminogen and bradykjnin were found at the middle of the tablet cycle. These levels were significantly higher than those found at the middle of the menstrual cycle. Blood level of fibrinogen was significantly reduced in females using pills, compared to the control group at the middle of both cycles. A marked elevation of plasminogen and bradvkinin levels was associated with proportionate decrease in the level of fibrinogen in dry socket eases. The difference between the control and pill users groups was significant