Impairment of maturation of BMP-6 (35 kDa) correlates with delayed fracture healing in experimental diabetes

TY - JOUR

T1 - Impairment of maturation of BMP-6 (35 kDa) correlates with delayed fracture healing in experimental diabetes

AU - Guo, Qidong

AU - Wang, Weijie

AU - Abboud, Rami

AU - Guo, Zheng

N1 - This work was supported by the National Natural Science Foundation of China (30471656, 30772083, 30972860 to Z.G.).

PY - 2020/12

Y1 - 2020/12

N2 - 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 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.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.

AB - 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 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.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.

KW - BMP-6

KW - Delayed union

KW - Diabetes

KW - Fracture

KW - Healing

KW - Nonunion

U2 - 10.1186/s13018-020-01705-7

DO - 10.1186/s13018-020-01705-7

M3 - Article

C2 - 32448307

SN - 1749-799X

VL - 15

JO - Journal of Orthopaedic Surgery and Research

JF - Journal of Orthopaedic Surgery and Research

IS - 1

M1 - 186

ER -