Abstract
Background: Although it is known that diabetes interferes with fracture healing, the mechanisms remain poorly understood. The aim of this study was to investigate the correlation of BMP-6 and BMP-9 with the impairment in fracture healing in diabetes, by analyses of the difference in size and calcification of the callus, mechanical endurance and expressing BMP-6 and BMP-9 in the callus, using a clinical related diabetic rodent model. Methods: We evaluated femur fracture healing by quantification of size and calcification of the callus by X-ray, histological and histochemical images, loading capacity of the fractured bone and amount of BMP-6 in the callus and the bones using Western blot assay. Results: Significant upregulation of BMP-6 in the callus and the fractured bones of both non-diabetic and the diabetic animals was observed, at the end of the 2nd and the 4th weeks after fracture. However, significantly lower levels of BMP-6 at 35kDa with smaller sizes of calcified callus and poor loading capacity of the healing bones were detected in the diabetic animals, compared to the non-diabetic controls. The impairment of the maturation procedure of BMP-6 (35 kDa) from precursors may be underlying the downregulation of the BMP-6 in diabetic animals. Conclusions: It could be concluded that the delayed fracture healing in the diabetic animals is correlated with deficiency of BMP-6 (35 kDa), which may be caused by impairment of maturation procedure of BMP-6 from precursors to functioning format. This is a primary study but an important step to explore the molecular pathogenesis of impairment of fracture healing in diabetes and to molecular therapeutic approach for the impairment of fracture healing.