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Research article
Impairment of maturation of BMP-6 (35kDa) correlates with delayed fracture healing in experimental diabetes
Zheng Guo
Second Hospital of Shanxi Medical University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-2294-3873
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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.
Keywords
BMP-6; delayed union; diabetes; fracture; healing; nonunion
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This preprint is under consideration at Journal of Orthopaedic Surgery and Research. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Impairment of maturation of BMP-6 (35kDa) correlates with delayed fracture healing in experimental diabetes
Zheng Guo
Second Hospital of Shanxi Medical University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-2294-3873
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 2
Posted 16 Apr, 2020
No community comments so far
Review #1 received
Received 28 Apr, 2020
Reviewer #2 agreed
On 17 Apr, 2020
Editor assigned
On 14 Apr, 2020
Reviewers invited
Invitations sent on 14 Apr, 2020
Reviewer #1 agreed
On 14 Apr, 2020
Submission checks complete
On 13 Apr, 2020
Editor invited
On 13 Apr, 2020
No comments provided
Editor assigned
On 06 Apr, 2020
Editorial decision: Revise before review
On 06 Apr, 2020
Editor invited
On 05 Apr, 2020
Submission checks complete
On 02 Apr, 2020
First submitted
On 30 Mar, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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.
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Figure 2
Figure 3
Figure 4
Figure 5
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