Abstract
BackgroundAlthough 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.MethodsWe 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.ResultsSignificant 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 second and the fourth weeks after fracture. However, significantly lower levels of BMP-6 at 35 kDa 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.ConclusionsIt 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.
Highlights
It is known that diabetes interferes with fracture healing, the mechanisms remain poorly understood
A considerable effort has been made to identify the impact of diabetes on osteoblasts and bone formation [9,10,11], there have been few studies that investigate the molecular mechanism by which diabetes affects the process of fracture healing [12, 13]
We investigated the difference in expressions of Bone morphogenetic protein (BMP)-6 and BMP-9 in the healing femurs between diabetic and non-diabetic animal models, while the change in radiological, histological, and mechanical parameter was evaluated, making an attempt to reveal molecular pathological impact of BMP-6 and BMP-9 on the fracture healing
Summary
It is known that diabetes interferes with fracture healing, the mechanisms remain poorly understood. Cumulating evidence indicates that diabetes impairs bone health and fracture healing [2]. The mechanism underlying the nonunion was thought to be mainly associated with severity of injury in the fracture site and the mode of surgical treatment [7, 8]. A considerable effort has been made to identify the impact of diabetes on osteoblasts and bone formation [9,10,11], there have been few studies that investigate the molecular mechanism by which diabetes affects the process of fracture healing [12, 13]. Exploring the molecular, pathogenetic changes in the healing bone in diabetes is important for further understanding of the pathology of impairment of the fracture union
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