Efeito do diabetes tipo 1 na neoformação óssea em defeitos críticos em fêmur de camundongos : relevância dos receptores b1 das cininas

Abstract

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