Made available in DSpace on 2015-04-14T13:30:31Z (GMT). No. of bitstreams: 1 456861.pdf: 2147908 bytes, checksum: b9bc5ecae0f349a191f0641931e9e7d7 (MD5) Previous issue date: 2014-02-26 / The effects on kinin B1 receptor (B1R) deletion were examined on bone regeneration in streptozotocin (STZ)-type-1 diabetic mice, subjected to a model of femoral critical-size defect. Diabetes induction in wild-type C57/BL6 (WT C57/BL6) mice was allied to decrease of body weight and hyperglycemia, in relation to the non-diabetic group of the same strain. The lack of B1R did not affect STZ-elicited body weight loss, although it partially prevented hyperglycemia. Type-1 diabetic mice presented a clear delay in bone regeneration, with large areas of loose connective tissue within the region corresponding to the defects, when compared to wide areas of newly-formed woven bone in non-diabetic WT C57/BL6 mice. Notably, either non-diabetic or diabetic B1R knockout (B1RKO) mice displayed bone regeneration levels comparable to that seen in control WT C57/BL6 mice. The improved bone regeneration in animals lacking B1R was further confirmed by analysis of collagen contents. WT C57/BL6 STZ-diabetic mice presented a marked reduction of collagen contents within the bone defect gap, whereas diabetic B1RKO displayed collagen levels comparable to those observed in non-diabetic WT C57/BL6 or B1RKO mice. The enhanced bone regeneration in diabetic mice lacking B1R does not seem to be associated to lessened osteoclast activity, as no prominent difference was detected in the levels of tartrate-resistant acid phosphatase (TRAP) positivity, or even in the immunolabeling for the proteins of the RANK/RANKL/OPG system thoughout all the experimental groups. Data brings novel evidence on the relevance of B1R under type-1 diabetes, especially concerning its role in bone regeneration after surgical procedures / Os efeitos da dele??o g?nica do receptor B1 das cininas na regenera??o ?ssea foram avaliados em camundongos com diabetes tipo 1 induzida por estreptozotocina, submetidos a um modelo de defeito cr?tico no f?mur. Como resultado da indu??o de diabetes nos camundongos wild-type C57/BL6, houve um decr?scimo do peso corporal e hiperglicemia em rela??o ao grupo n?o-diab?tico da mesma cepa. Os animais diab?ticos, com aus?ncia do receptor B1 apresentaram perda do peso corporal e, uma preven??o parcial da hiperglicemia. Camundongos diab?ticos do tipo 1 tiveram um atraso na regenera??o ?ssea, apresentando um tecido conectivo desorganizado na regi?o correspondente ao defeito cr?tico, quando comparados a extensas ?reas de tecido ?sseo rec?m-formado em camundongos WT C57/BL6 n?o diab?ticos. Camundongos B1R nocaute, diab?ticos ou n?o diab?ticos, exibiram n?veis de regenera??o ?ssea semelhantes aos observados no grupo controle WT C57/BL6. A melhora na regenera??o ?ssea nos animais sem o receptor B1 foi confirmada pela an?lise da quantidade de col?geno. Camundongos WT C57/BL6 diab?ticos apresentaram uma redu??o acentuada da distribui??o de col?geno na regi?o do defeito ?sseo, enquanto que os animais B1RKO diab?ticos exibiram n?veis de col?geno similares ?queles observados nos camundongos n?o diab?ticos, tanto WT C57/BL6, quanto B1RKO. A melhora da regenera??o ?ssea nos camundongos diab?ticos sem o receptor B1 n?o parece estar associado ? atividade osteocl?stica diminu?da. Ademais, nenhuma diferen?a marcante foi encontrada nos n?veis de fosfatase ?cida resistente ao tartarato (TRAP) ou, na imunomarca??o para as prote?nas do sistema RANK/RANKL/OPG, em todos grupos experimentais avaliados. Os resultados deste trabalho fornecem novas evid?ncias a respeito da relev?ncia dos receptores B1 no diabetes do tipo 1, especialmente no que diz respeito ao seu papel na regenera??o ?ssea ap?s procedimentos cir?rgicos