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

Qidong Guo, Weijie Wang, Rami Abboud, Zheng Guo (Lead / Corresponding author)

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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 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.

Original languageEnglish
Article number186
Pages (from-to)1-11
Number of pages11
JournalJournal of orthopaedic surgery and research
Volume15
Issue number1
Early online date24 May 2020
DOIs
Publication statusE-pub ahead of print - 24 May 2020

Keywords

  • BMP-6
  • Delayed union
  • Diabetes
  • Fracture
  • Healing
  • Nonunion

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