Os benefícios à saúde relacionados ao consumo moderado de vinho incluem diferentes mecanismos, nos quais estão envolvidos tanto etanol quanto compostos fenólicos que são constituintes do mesmo. Com o objetivo de avaliar variações glicêmicas, ponderais e o depósito de triglicérides, colesterol e glicogênio hepáticos com uso regular de vinho tinto em camundongo ApoE Knockout, foram utilizados 60 camundongos machos adultos ApoE Knockout de peso médio de 30 gramas, distribuídos em três grupos de 20 animais: grupo vinho, grupo etanol e grupo água, os quais receberam 50 mL de vinho e 50 mL água, 6mL de etanol e 94mL de água e somente água respectivamente por quatro meses. Os parâmetros avaliados foram: variações glicêmicas, ponderais, acúmulo de triglicerídeos, colesterol e glicogênio hepáticos. O grupo vinho teve em relação a sua massa corporal uma área sob a curva maior que a dos outros dois grupos, mas com um percentual pequeno de aumento. A concentração do triglicerídeo hepático foi maior no grupo vinho 57% em relação ao grupo etanol, que foi 31,6% menor que o controle (p<0,01%). A concentração do colesterol hepático foi menor no grupo vinho (23,6%), assim como no grupo etanol (24,5%), (p<0,05%). A concentração do glicogênio hepático foi maior no grupo vinho (16%), porém não alcançando significado estatístico. A glicemia em jejum no dia da eutanásia foi maior no grupo etanol em relação aos demais grupos, porém não demonstrou diferença estatisticamente significante. Na análise histológica não foi observada diferença significativa entre os grupos, embora o peso médio em gramas nas gorduras, retroperitoneal e subcutâneas tenha sido aproximadamente duas vezes maior no grupo vinho. Concluiu-se que neste estudo o uso regular e crônico de vinho tinto aumentou triglicerídeo hepático, porém o álcool diminui o colesterol hepático. O aumento do triglicerídeo pode ser devido ao alto valor calórico do vinho ou alguma propriedade lipogênica desconhecida que levou ao aumento importante das gorduras retroperitoneais e subcutâneas em camundongos ApoE Knockout. / The benefits to health related to regular consume of red wine includes different mechanisms in which are involved both ethanol and fenolics compounds of the wine. With the objective to evaluate glycemia, lipid profile and weight variations with regular use of red wine by ApoE Knockout mices, sixty adults ApoE Knockout mices weighing around 30g were distributed into 3 groups of 20 animals each: 1.Wine that received 50mL of wine plus 50mL of water, 2. Ethanol and Water groups, 6mL of ethanol plus 94mL of water and just water respectively for 4 months. We evaluate glycemia, weight variations and liver glycogen, triglycerides and cholesterol. The wine group had in relation to its mass body an area under the curve larger than the other two groups, but with a small percentage of increase. The concentration of liver triglycerides was higher in the wine 57% compared to ethanol group, which was 31.6% lower than the control (p<0.01%). The concentration of liver cholesterol was lower in wine (23.6%) and in ethanol group (24.5%) (p<0.05%). The liver glycogen concentration was higher in the wine (16%), although not reaching statistical significance. The fasting glicemia on the day of euthanasia was higher in the ethanol group compared to other groups, but not statistically significant difference. In histological analysis was not significantly different between groups, although the average weight in grams fat, retroperitoneal and subcutaneous was approximately two times higher in the wine group. It was concluded that in this study the regular and chronic use of red wine increased liver triglyceride, however alcohol decreases liver cholesterol. The increase of the triglyceride may be due to the high caloric value of wine or some lipogenic unknown property that led to an important increase in retroperitoneal and subcutaneous fat tissue in ApoE Knockout mice.

Os benefícios à saúde relacionados ao consumo moderado de vinho incluem diferentes mecanismos, nos quais estão envolvidos tanto etanol quanto compostos fenólicos que são constituintes do mesmo. Com o objetivo de avaliar variações glicêmicas, ponderais e o depósito de triglicérides, colesterol e glicogênio hepáticos com uso regular de vinho tinto em camundongo ApoE Knockout, foram utilizados 60 camundongos machos adultos ApoE Knockout de peso médio de 30 gramas, distribuídos em três grupos de 20 animais: grupo vinho, grupo etanol e grupo água, os quais receberam 50 mL de vinho e 50 mL água, 6mL de etanol e 94mL de água e somente água respectivamente por quatro meses. Os parâmetros avaliados foram: variações glicêmicas, ponderais, acúmulo de triglicerídeos, colesterol e glicogênio hepáticos. O grupo vinho teve em relação a sua massa corporal uma área sob a curva maior que a dos outros dois grupos, mas com um percentual pequeno de aumento. A concentração do triglicerídeo hepático foi maior no grupo vinho 57% em relação ao grupo etanol, que foi 31,6% menor que o controle (p<0,01%). A concentração do colesterol hepático foi menor no grupo vinho (23,6%), assim como no grupo etanol (24,5%), (p<0,05%). A concentração do glicogênio hepático foi maior no grupo vinho (16%), porém não alcançando significado estatístico. A glicemia em jejum no dia da eutanásia foi maior no grupo etanol em relação aos demais grupos, porém não demonstrou diferença estatisticamente significante. Na análise histológica não foi observada diferença significativa entre os grupos, embora o peso médio em gramas nas gorduras, retroperitoneal e subcutâneas tenha sido aproximadamente duas vezes maior no grupo vinho. Concluiu-se que neste estudo o uso regular e crônico de vinho tinto aumentou triglicerídeo hepático, porém o álcool diminui o colesterol hepático. O aumento do triglicerídeo pode ser devido ao alto valor calórico do vinho ou alguma propriedade lipogênica desconhecida que levou ao aumento importante das gorduras retroperitoneais e subcutâneas em camundongos ApoE Knockout. / The benefits to health related to regular consume of red wine includes different mechanisms in which are involved both ethanol and fenolics compounds of the wine. With the objective to evaluate glycemia, lipid profile and weight variations with regular use of red wine by ApoE Knockout mices, sixty adults ApoE Knockout mices weighing around 30g were distributed into 3 groups of 20 animals each: 1.Wine that received 50mL of wine plus 50mL of water, 2. Ethanol and Water groups, 6mL of ethanol plus 94mL of water and just water respectively for 4 months. We evaluate glycemia, weight variations and liver glycogen, triglycerides and cholesterol. The wine group had in relation to its mass body an area under the curve larger than the other two groups, but with a small percentage of increase. The concentration of liver triglycerides was higher in the wine 57% compared to ethanol group, which was 31.6% lower than the control (p<0.01%). The concentration of liver cholesterol was lower in wine (23.6%) and in ethanol group (24.5%) (p<0.05%). The liver glycogen concentration was higher in the wine (16%), although not reaching statistical significance. The fasting glicemia on the day of euthanasia was higher in the ethanol group compared to other groups, but not statistically significant difference. In histological analysis was not significantly different between groups, although the average weight in grams fat, retroperitoneal and subcutaneous was approximately two times higher in the wine group. It was concluded that in this study the regular and chronic use of red wine increased liver triglyceride, however alcohol decreases liver cholesterol. The increase of the triglyceride may be due to the high caloric value of wine or some lipogenic unknown property that led to an important increase in retroperitoneal and subcutaneous fat tissue in ApoE Knockout mice.

A insuficiência cardíaca (IC) é uma síndrome clínica de alta incidência e mau prognóstico, caracterizada por fadiga, dispnéia e grande limitação aos esforços físicos. Essas alterações não estão apenas limitadas ao comprometimento cardíaco, mas em parte, são decorrentes também de alterações morfo-funcionais da musculatura esquelética. Para a dissertação foram utilizados camundongos com deleção dos genes para os receptores ?2A e ?2C adrenérgicos (KO) que desenvolvem cardiomiopatia induzida por hiperatividade simpática, associada à sinais clínicos de IC e 50% de mortalidade aos sete meses de idade. Foi objetivo desse estudo realizar a caracterização fenotípica do músculo esquelético por meio de avaliações funcionais e morfológicas em camundongos KO previamente ao desenvolvimento da IC (três meses de idade), e ao longo de sua progressão (cinco e sete meses de idade). Somente na faixa etária de sete meses de idades foi constatado o estabelecimento da miopatia muscular esquelética. Nessa fase, observou-se rarefação vascular, atrofia muscular, aumento na porcentagem de fibras glicolíticas e redução na atividade máxima da enzima citrato sintase, que em conjunto, contribuem para a antecipação da fadiga observada nesse modelo, e como conseqüência, para a redução da tolerância aos esforços. Os resultados sugerem que os camundongos KO apresentam alterações morfo-funcionais da musculatura esquelética semelhantes às observadas nos demais modelos de IC e em indivíduos portadores dessa síndrome. Portanto, sendo um ótimo modelo experimental para estudos de futuras estratégias terapêuticas que visem minimizar as alterações na musculatura esquelética decorrentes da IC / Heart failure (HF) is a clinical syndrome with high incidence and bad prognostic, characterized by fatigue, dyspnea, and increased intolerance to exercise. These changes are not only related to the cardiovascular tissue, but are at least in part, consequence of morphofunctional alterations in skeletal muscles. To the present study it was used mice lacking both ?2A/?2C AR subtypes (KO) which develop cardiomyopathy induced by sympathetic hyperactivity, associated to clinical signals of HF and 50% of mortality at seven months of age. The aim of the present study was characterize the phenotype of skeletal muscle by functional and morphological evaluations in KO before (three months of age) and during the HF progression (five and seven months of age). Skeletal muscle alterations due HF were observed only at seven months of age. The alterations were characterized by vascular rarefaction, muscular atrophy, increase in glycolitic fibers percentage and reduction of maximal activity of citrate synthase and contributed with early fatigue observed in this model, and consequently, exercise intolerance. The results of present study suggest that KO mice present morphofunctional changes in skeletal muscles in a similarly to others models of HF and in patients that have this syndrome. Therefore, consisting in an excellent experimental model to future studies related to therapeutic strategies to minimize the skeletal muscle changes due HF

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Cannabinoids have been shown to alter synaptic plasticity but the mechanism by which this occurs at hippocampal CA3-CA1 synapses in vivo is not yet known. Utilizing in vivo electrophysiological recordings of field excitatory postsynaptic potentials (fEPSP) on anesthetized rats and mice as well as three lines of conditional knockout mouse models, the objective was to show a two-part mechanistic breakdown of cannabinoid-evoked CA3-CA1 long-term depression (LTD) in its induction as well as early and later-phase expression stages. It was determined that this cannabinoid-induced in vivo LTD requires cannabinoid type-1 receptors (CB1Rs) on astrocytes, but not CB1Rs on glutamatergic or GABAergic neuronal axons/terminals. Pharmacological testing determined that cannabinoid-induced in vivo LTD also requires activation of NMDA receptors (NMDAR) and subsequent postsynaptic endocytosis of AMPA receptors (AMPAR). There exists a clear role for NR2B-containing NMDARs in a persistent, transitory form, potentially related to prolonged or delayed glutamate release (possibly as a result of the astrocytic network). A key determination of the expression phase is the involvement of new protein synthesis (using translation and transcription inhibitors) – further evidence of the long-term action of the synaptic plasticity from a single cannabinoid dose.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

L'arthrose est une maladie articulaire dégénérative, avec une pathogenèse inconnue. Des études récentes suggèrent que l'activation du facteur de transcription du récepteur activateur de la prolifération des peroxysomes (PPAR) gamma est une cible thérapeutique pour ce maladie. Les agonistes du PPARγ inhibent l'inflammation et réduisent la synthèse des produits de dégradation du cartilage in vitro et in vivo. Cependant, des études utilisant des agonistes du PPARγ n’élucident pas les effets exacts médiés par ce gène complexe. En effet, certains de ces agonistes ont la capacité de régulariser d'autres voies de signalisation indépendantes de PPARγ, ainsi entraînant des effets secondaires graves. Afin d'obtenir une efficacité thérapeutique avec potentiellement moins de problèmes de sécurité, il est donc essentiel d'élucider, in vivo, le rôle exact de PPARγ dans la physiopathologie OA. Mon projet de thèse permettra de déterminer, pour la première fois, le rôle spécifique de PPARγ in vivo dans la physiopathologie OA. Les souris utilisées pour l’étude avaient une délétion conditionnelle du gène PPARγ dans le cartilage. Ces dernières ont été générées en employant le système LoxP/Cre. Pour tester cette hypothèse, j'ai généré deux types de souris avec une délétion au PPARγ, (a) une suppression du gène PPARγ spécifiquement dans le cartilage germinale pour l'étude de l'arthrose liée au développement et à l'âge et (b) la suppression inductible du gène PPARγ spécifiquement dans le cartilage chez la souris adulte pour les études OA. L’étude précédente dans notre laboratoire, utilisant ces souris ayant une délétion au gène PPARγ germinales, montre que ces souris présentent des anomalies du développement du cartilage. J'ai également exploré si ces souris qui présentent des défauts précoces du développement ont toutes les modifications phénotypiques dans le cartilage au cours du vieillissement. Mes résultats ont montré que les souris adultes, ayant une délétion au gène PPARγ, ont présenter un phénotype de l'arthrose spontanée associée à une dégradation du cartilage, l’hypocellularité, la fibrose synoviale. Cette étude a montré que PPARγ est un régulateur essentiel pour le cartilage, et c’est le manque (l’absence) de ce dernier qui conduit à un phénotype de l'arthrose spontanée accélérée (American Journal of Pathologie). A partir de ce but de l'étude, on n’a pas pu vérifier si ces souris présentaient l’OA spontanée en raison des défauts de développement ou à la suite de la délétion du gène PPARγ. Pour contourner les défauts de développement, j'ai généré des souris ayant une délétion du gène PPARγ spécifiquement dans le cartilage inductible avec le système Col2rTACre. Ces souris ont été soumises à modèle de la chirurgie OA (DMM: déstabilisation du ménisque médial) et les résultats révèlent que les souris PPARγ KO ont une dégradation accélérée du cartilage, une hypocellularité, une fibrose synoviale et une augmentation de l'expression des marqueurs cataboliques et des marqueurs inflammatoire. La perte de PPAR dans le cartilage articulaire est un évènement critique qui initie la dégradation de cartilage dans OA. Les études récentes suggèrent que le procès d’autophagie, une forme de survie cellulaire programmée, est altéré pendant l’OA et peut contribuer vers une protection diminuée des cellules, résultant la dégradation du cartilage. J’ai donc exploré le rôle de PPARγ dans la protection des cellules en déterminant l’effet de manque de PPARγ dans le cartilage par l’expression de mTOR (régulateur négatif principal d’autophagie) et les gènes d’autophagie durant OA. Mes résultats ont montré que les souris KO PPARγ présentent également une augmentation sur l'expression de mTOR et une diminution sur l’expression des marqueurs autophagiques en comparaison avec les chondrocytes articulaires isolés des souris contrôles OA. J'ai suggéré l'hypothèse que PPARγ contrôle la régulation de la signalisation de mTOR/autophagie, et finalement la mort des chondrocytes et l’expression des facteurs cataboliques et les facteurs inflammatoire. Pour tester cette hypothèse, j’ai fait la transfection des chondrocytes arthrosiques PPARγ-KO avec le vecteur d’expression de PPARγ pour déterminer si la restauration de l'expression de PPARγ peut sauver le phénotype des cellules PPARγ-KO OA. J'ai observé que la restauration de l'expression de PPARγ dans les cellules PPARγ-KO en présence du vecteur d'expression PPARγ, a pu considérablement régulariser négativement l'expression de mTOR et mettre en règle positivement l'expression des gènes autophagiques ainsi que le sauvetage significative de l'expression du collagène de type II et l’aggrecan et de baisser de manière significative l'expression de marqueurs cataboliques critiques et des marqueurs inflammatoires. Pour prouver que l’augmentation de la signalisation de mTOR et la diminution de l'autophagie est responsable du phénotype OA accélérée observée dans les souris PPARγ KO in vivo, j'ai généré les souris doubles KO PPARγ- mTOR inductible spécifique du cartilage en utilisant le système Col2 - rtTA -Cre et soumis ces souris à DMM modèle de l'arthrose. Mes résultants démontrent que les souris avec PPARγ- mTOR doubles KO ont été significativement protégés contre les OA DMM induites associées à une protection significative contre la destruction du cartilage, la perte de protéoglycanes et la perte de chondro-cellularité par rapport aux souris témoins. Considérant que mTOR est un répresseur majeur de l'autophagie, j'ai trouvé que l'expression de deux marqueurs de l'autophagie critiques (ULK1 et LC3B) a été significativement plus élevée dans les chondrocytes extraits les souris doubles KO PPARγ-mTOR par rapport aux souris témoins. En plus, les études de sauvetage in vitro en utilisant le vecteur d'expression PPAR et les études in vivo utilisant les souris doubles KO PPARγ- mTOR montrent que PPARγ est impliqué dans la régulation de la protéine signalant de mTOR/autophagie dans le cartilage articulaire. Ces résultats contournent PPARγ et sa signalisation en aval de mTOR/autophagie en tant que cibles thérapeutiques potentielles pour le traitement de l'arthrose. / Osteoarthritis (OA) is an age related degenerative joint disease with unknown pathogenesis. Recent studies suggest that the activation of the transcription factor Peroxisome Proliferator-Activated Receptor gamma (PPARγ) is a therapeutic target for OA. Agonists of PPARγ inhibit inflammation and reduce the synthesis of cartilage degradation products both in vitro and in vivo. However, studies using agonists of PPARγ do not elucidate the exact effects mediated by this complex gene. Indeed, some of these agonists have the ability to regulate, in vivo, various other signaling pathways independent of PPARγ, resulting in serious side effects. It is therefore vital, in order to achieve therapeutic efficacy with potentially less safety concerns, to elucidate the exact in vivo role of PPARγ in OA pathophysiology. Thus, the aim of my PhD project was to determine the specific in vivo role of PPARγ in OA pathophysiology using cartilage-specific PPARγ knockout (KO) mice and subjecting these mice to surgical model of OA. I generated two separate PPARγ KO mice harboring a (a) constitutive cartilage-specific germ-line deletion of PPARγ gene for developmental and age-related OA study and (b) inducible cartilage-specific deletion of PPARγ in adult mouse specifically for OA studies using LoxP Cre system. Previous study in my laboratory using germ-line PPARγ KO mice shows that these mice exhibit cartilage developmental defects. I further explored if these mice which exhibit early developmental defects have any phenotypic changes in the articular cartilage during ageing. My results showed that adult PPARγ KO mice exhibited a spontaneous OA phenotype associated with enhanced cartilage degradation, hypocellularity, synovial fibrosis, and increased expression of catabolic and inflammatory factors. This study showed that PPARγ is a critical regulator of cartilage health, the lack of which leads to an accelerated spontaneous OA phenotype (Vasheghani et al, 2013; American Journal of Pathology). From this aim of the study, I could not ascertain if cartilage-specific germline PPARγ KO mice exhibited spontaneous OA because of developmental defects or as a result of PPARγ deficiency. To bypass the developmental defects, I then generated inducible cartilage-specific PPARγ KO mice using Col2rTACre system and subjected these mice to destabilization of medial meniscus (DMM) model of OA surgery. My results revealed that PPARγ KO mice showed accelerated cartilage degradation, hypo-cellularity, synovial fibrosis and increased expression of catabolic and inflammatory factors during OA. Loss of chondrocyte cellularity within the articular cartilage is one of the critical events that initiate the degradation of the cartilage during OA. Recent studies suggest that the process of autophagy, a form of programmed cell survival, is impaired during OA and may contribute towards decreased chondro-protection resulting in cartilage degradation. Thus, I further explored the role of PPARγ in chondro-protection by determining the effect of PPARγ deficiency in the cartilage on the expression of mTOR (master negative regulator of autophagy) and autophagy genes during OA. My results revealed that PPARγ-deficient chondrocytes exhibit significantly enhanced expression of mTOR and decreased expression of genes that initiate autophagy process compared to chondrocytes extracted from control OA mice. I then hypothesized that PPARγ controls mTOR/autophagy signaling and ultimately the fate of chondrocytes and the expression of catabolic and inflammatory factors in the articular cartilage. To test this, I transfected PPARγ KO OA chondrocytes with PPARγ expression vector to determine if restoration of PPARγ expression can rescue the phenotype of PPARγ KO OA cells. I observed that restoration of PPARγ expression in PPARγ KO cells significantly down-regulated the expression of mTOR and up-regulate the expression of autophagy genes along with significant rescue in the expression of collagen type II and aggrecan and significant down-regulation in the expression of critical catabolic and inflammatory markers. To validate our in vitro finding that enhanced mTOR signalling and resultant decrease in autophagy is responsible for accelerated OA phenotype observed in PPARγ KO mice, I generated inducible cartilage-specific PPARγ-mTOR double KO mice and subjected these mice to DMM model of OA. My results clearly demonstrate that PPARγ-mTOR double KO mice exhibit significant protection against DMM-induced OA associated with significant protection from cartilage destruction, proteoglycan loss and loss of chondro-cellularity compared with control mice. Since mTOR is a major repressor of autophagy, I found that the expression of two critical autophagy markers (ULK1 and LC3B) was significantly elevated in PPARγ-mTOR double KO mice compared to control mice. My in vitro rescue studies using PPARγ expression vector and in vivo studies using PPARγ- mTOR double KO mice clearly show that PPARγ is involved in the regulation of mTOR/autophagy signalling in the articular cartilage. Therefore, deficiency of PPARγ upregulates mTOR signalling resulting in the suppression of autophagy and decreased chondroprotection and increased catabolic activity leading to accelerated severe OA. This study for the first time provides direct evidence on the role of PPARγ in chondroprotection by modulation of mTOR/autophagy signalling in the articular cartilage. These findings outline PPARγ and its downstream signalling by mTOR/autophagy as potential therapeutic targets for the treatment of OA.

Introdução: O objetivo deste trabalho foi caracterizar a composição da microbiota bucal e a formação e progressão de lesões periapicais induzidas experimentalmente em dentes de camundongos knockout para IL-22 (IL-22 KO) comparados com animais wild-type (WT). Material e Métodos: Inicialmente, foi realizada a avaliação do perfil microbiano da cavidade bucal dos animais (40 espécies de micro-organismos), no dia das exposições pulpares, por meio de técnica de biologia molecular (Checkerboard DNA-DNA hybridization). Em seguida, lesões periapicais foram induzidas nos primeiros molares inferiores dos camundongos e, decorridos os períodos de 7, 21 e 42 dias, os animais foram submetidos à eutanásia em câmara de CO2. As mandíbulas foram então removidas e submetidas ao processamento histotécnico. A seguir, cortes representativos de cada dente foram corados com hematoxilina e eosina (HE), para descrição do tecido pulpar e das regiões apical e periapical, em microscopia óptica convencional e mensuração da área das lesões periapicais em microscopia de fluorescência. Além disso, cortes sequenciais foram avaliados por meio de: histoenzimologia para a marcação de osteoclastos (TRAP), coloração de Brown & Brenn (para identificação de bactérias) e imunohistoquímica (para identificação de RANK, RANKL e OPG). Os escores da quantidade de células bacterianas, para cada uma das 40 espécies avaliadas, foram submetidos à analise estatística empregando o teste não-paramétrico de Mann-Whitney para amostras independentes, para comparação entre os grupos. Os resultados numéricos obtidos na análise morfométrica da área das lesões periapicais e do número de osteoclastos foram submetidos à análise estatística \"one-way\" ANOVA e pós-teste de Bonferroni. Para todas as análises foi adotado o nível de significância de 5%. Resultados: Em relação ao perfil microbiano encontrado na cavidade bucal dos animais, foi possível observar diferença estatisticamente siginificante entre os dois grupos de animais para 6 espécies bacterianas (p<0,05), sendo 5 dessas espécies mais encontradas nos animais WT e apenas 1 encontrada em maior quantidade nos animais IL-22 KO. Já em relação à análise microscópica, o grupo dos animais WT mostrou diferença estatisticamente significante entre 7 e 42 dias e entre 21 e 42 dias, com aumento progressivo no tamanho das lesões e no número de osteoclastos (p<0,05). No grupo dos animais IL-22 KO, houve um aumento do tamanho da lesão e do número de osteoclastos entre 7 e 21 dias, seguido de diminuição desses parâmetros entre 21 e 42 dias, com diferença significante (p<0,05) entre 7 e 21 dias. Além disso, na comparação entre os dois tipos de animais, foram encontradas diferenças significantes (p<0,05) em relação ao tamanho das lesões periapicais e ao número de osteoclastos aos 42 dias, sem diferenças em relação à localização de bactérias e imunohistoquímica. Conclusões: Esse estudo demonstrou diferenças na composição da microbiota bucal dos animais WT e IL-22 KO, o que pode ter influenciado na formação das lesões periapicais. Além disso, a ausência da IL-22 em camundongos interferiu na progressão das lesões periapicais, assim como no número de osteoclastos, sugerindo a participação da IL-22 na resposta imune e inflamatória do hospedeiro à infecção dos canais radiculares. / Introduction: The aim of this study was to evaluate the participation of the IL-22 on the formation and progression of experimentally induced periapical lesions in teeth of IL-22 knockout (IL-22 KO) compared to wild-type (WT) mice. Methods: Initially, it was performed the evaluation of the microbial profile present in the oral cavity of animals (40 bacterial species), on the day of pulpal exposures, by means of molecular biology technique (checkerboard DNA-DNA hybridization). Then, the periapical lesions were induced in the inferior first molars of the mice and, after the periods of 7, 21 and 42 days, the animals were euthanized in a CO2 chamber. The jaws were removed and subjected to histotechnical processing. The following sections were representative stained with hematoxylin and eosin (HE) for description of the pulp tissue, apical and periapical regions in conventional optical microscopy and measurement of the area of periapical lesions in fluorescence microscopy. Moreover, sequential specimens were evaluated through: histoenzimology for osteoclasts (TRAP) Brown & Brenn staining (for bacteria identification) and immunohistochemistry (for RANK, RANKL and OPG identification). The scores of the amount of bacterial cells, for each one of the 40 species assessed, were subjected to statistical analysis using the nonparametric Mann-Whitney test for independent samples for comparison between groups. The numerical results of the morphometric analysis of the area of the periapical lesions and the number of osteoclasts were subjected to statistical analysis one-way ANOVA and Bonferroni\'s post-test. For all the statistical analysis the significance level of 5% was adopted. Results: Regarding the microbial profile found in the oral cavity of the animals, it was observed statistically siginificant differences between the two groups of animals for 6 bacterial species (p<0.05), with 5 species showing higher levels in the WT group and only 1 specie found in higher levels in the IL-22 KO animals. Concerning the microscopical analysis, the group of WT mice showed a statistically significant difference between 7 and 42 days and between 21 and 42 days, with a gradual increase in the size of periapical lesions and number of osteoclasts (p<0.05). In the group of IL-22 KO animals, an increase in lesion size and number of osteoclasts between 7 and 21 days was observed, followed by a decrease of these parameters between 21 and 42 days, with significant differences between 7 and 21 days (p <0.05). Moreover, when comparing the two types of animals, significant differences were found (p <0.05) about to the size of periapical lesions and number of osteoclasts at 42 days, without differences in localization of bacteria and immunohistochemistry. Conclusions: This study showed differences in the composition of the oral microbiota of the two types of animals that may have influenced the progression of periapical lesions. Moreover, the absence of IL-22 in mice interfered with the progression of periapical lesions, as well as in the number of osteoclasts, suggesting the involvement of this cytokine in host\'s immune and inflammatory response to the infection of root canals.