Kinin B1 Receptor Deletion Affects Bone Healing in Type 1 Diabetic Mice

• Published in: Journal of cellular physiology 2015-12, Vol.230 (12), p.3019-3028
• Main Authors: Cignachi, Natália P., Pesquero, João B., Oliveira, Rogério B., Etges, Adriana, Campos, Maria M.
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Body weight; Bone Regeneration; Caspase 3 - metabolism; Collagen - metabolism; Diabetes Mellitus, Experimental - genetics; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - pathology; Diabetes Mellitus, Experimental - physiopathology; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - metabolism; Diabetes Mellitus, Type 1 - pathology; Diabetes Mellitus, Type 1 - physiopathology; Femoral Fractures - genetics; Femoral Fractures - metabolism; Femoral Fractures - pathology; Femoral Fractures - physiopathology; Femur - metabolism; Femur - pathology; Femur - physiopathology; Fracture Healing; Male; Mice, Inbred C57BL; Mice, Knockout; Mineralization; Osteonectin - metabolism; Receptor, Bradykinin B1 - deficiency; Receptor, Bradykinin B1 - genetics; Signal Transduction; Time Factors
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.25034

The effects of kinin B1 receptor (B1R) deletion were examined on femur bone regeneration in streptozotocin (STZ)‐type 1 diabetes. Diabetes induction in wild‐type C57/BL6 (WTC57BL6) mice led to decrease in body weight and hyperglycemia, compared to the non‐diabetic group of the same strain. The lack of B1R did not affect STZ‐elicited body weight loss, but partially prevented hyperglycemia. Diabetic mice had a clear delay in bone regeneration, and displayed large areas of loose connective tissue within the defects, with a reduced expression of the mineralization‐related protein osteonectin, when compared to the non‐diabetic WTC57/BL6. The non‐diabetic and diabetic B1R knockout (B1RKO) mice had bone regeneration levels and osteonectin expression comparable to that seen in control WTC57/BL6 mice. WTC57/BL6 STZ‐diabetic mice also showed a marked reduction of collagen contents, with increased immunolabeling for the apoptosis marker caspase‐3, whereas diabetic B1RKO had collagen levels and caspase‐3 activity comparable to those observed in non‐diabetic WTC57/BL6 or B1RKO mice. No significant difference was detected in the number of tartrate‐resistant acid phosphatase (TRAP)‐stained cells, or in RANK/RANKL/OPG system immunolabeling throughout the experimental groups. Data bring novel evidence on the relevance of kinin B1R under type 1 diabetes with regards to its role in bone regeneration. J. Cell. Physiol. 230: 3019–3028, 2015. © 2015 Wiley Periodicals, Inc.