Tibial cortex transverse transport potentiates diabetic wound healing via activation of SDF-1/CXCR4 signaling

PeerJ. 2023 Sep 15:11:e15894. doi: 10.7717/peerj.15894. eCollection 2023.

Abstract

Background: The current treatments for diabetic foot ulcers have disadvantages of slow action and numerous complications. Tibial cortex transverse transport (TTT) surgery is an extension of the Ilizarov technique used to treat diabetic foot ulcers, and can shorten the repair time of diabetic foot ulcers. This study assessed the TTT technique for its effectiveness in healing diabetic foot ulcer skin lesions and its related molecular mechanisms.

Methods: Diabetic rat models were established by injecting healthy Sprague-Dawley rats with streptozotocin (STZ). The effects of TTT surgery on the model rats were assessed by recording changes in body weight, analyzing skin wound pictures, and performing H&E staining to assess the recovery of wounded skin. The numbers of endothelial progenitor cells (EPCs) in peripheral blood were analyzed by flow cytometry, and levels of CXCR4 and SDF-1 expression were qualitatively analyzed by immunofluorescence, immunohistochemistry, qRT-PCR, and western blotting.

Results: Both the histological results and foot wound pictures indicated that TTT promoted diabetic wound healing. Flow cytometry results showed that TTT increased the numbers of EPCs in peripheral blood as determined by CD34 and CD133 expression. In addition, activation of the SDF-1/CXCR4 signaling pathway and an accumulation of EPCs were observed in skin ulcers sites after TTT surgery. Finally, the levels of SDF-1 and CXCR4 mRNA and protein expression in the TTT group were higher than those in a blank or fixator group.

Conclusion: TTT promoted skin wound healing in diabetic foot ulcers possibly by activating the SDF-1/CXCR4 signaling pathway.

Keywords: Diabetic foot ulcers; SDF-1/CXCR4 signaling pathway; Tibial transverse bone transport; Wound healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD34
  • Blotting, Western
  • Diabetes Mellitus*
  • Diabetic Foot*
  • Rats
  • Rats, Sprague-Dawley
  • Wound Healing

Substances

  • Antigens, CD34

Associated data

  • figshare/10.6084/m9.figshare.22672939.v1

Grants and funding

This work was supported by the National Natural Science Foundation of China (No. 81972083), Science and Technology Planning Project of Guangzhou (Nos. 202102080052, 202102010057 and 202201020303), and the Science Foundation of Guangdong Second Provincial General Hospital (Nos. YQ2019-009, 3D-A2020002, and 3D-A2020004). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.