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Background <p>Diabetic wounds are characterized by impaired angiogenesis and disordered extracellular matrix remodeling, resulting in delayed repair. Bone marrow mesenchymal stem cells (BMSCs) promote wound healing mainly through paracrine mechanisms, but their function may be weakened in the diabetic microenvironment. Mechanical stimulation is an important biophysical cue that regulates stem cell behavior and secretion. This study investigated whether cyclic mechanical stretch enhances BMSC paracrine activity through a periostin (Postn)-associated Wnt/β-catenin pathway and improves diabetic wound healing.</p> Methods <p>BMSCs were subjected to cyclic stretch at 15% strain and 0.5&#xa0;Hz for 10&#xa0;h. Postn, Wnt/β-catenin pathway-related proteins, and paracrine factors, including VEGF, TGF-β1, and bFGF, were examined by qRT-PCR, Western blotting, and ELISA. si-Postn, XAV-939-mediated Wnt/β-catenin inhibition, and recombinant Postn rescue experiments were performed to clarify the underlying mechanism. Conditioned medium (CM) from different BMSC groups was used to treat rat umbilical vein endothelial cells and fibroblasts to assess migration and tube formation. The therapeutic effects of CM were further evaluated in a full-thickness diabetic rat wound model.</p> Results <p>Cyclic mechanical stretch increased BMSC spreading, altered F-actin organization, upregulated Postn expression, and promoted β-catenin nuclear accumulation. Mechanical stimulation also enhanced the expression of Wnt/β-catenin pathway-related proteins and increased the secretion of VEGF, TGF-β1, and bFGF. si-Postn attenuated Wnt/β-catenin activation and reduced the mechanically induced enhancement of paracrine factor secretion, whereas recombinant Postn supplementation partially restored these effects. Similarly, XAV-939-mediated inhibition of Wnt/β-catenin signaling suppressed the paracrine response of stretched BMSCs. Functionally, CM from mechanically stimulated BMSCs promoted endothelial cell migration, tube formation, and fibroblast migration in vitro, while these effects were weakened by Postn silencing or Wnt/β-catenin inhibition. In vivo, CM from stretched BMSCs accelerated diabetic wound repair, enhanced angiogenesis, and improved extracellular matrix organization and collagen maturation, whereas Postn silencing or Wnt/β-catenin inhibition reduced these therapeutic effects.</p> Conclusion <p>Cyclic mechanical stretch enhances the paracrine function of BMSCs through a Postn-associated Wnt/β-catenin signaling pathway. Conditioned medium derived from mechanically stimulated BMSCs promotes angiogenesis and matrix remodeling in diabetic wounds, suggesting a mechanobiology-based, cell-free therapeutic strategy for diabetic wound repair.</p>

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Mechanical stimulation activates Postn-mediated Wnt/β-catenin pathway to enhance BMSCs paracrine function and promote wound healing in diabetic rats

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月31日

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  • Dong Zhang,
  • Haowei Zhou,
  • Congying Zhao,
  • Zhanjun Lei,
  • Zhe Liu,
  • Junwei Su,
  • Gaoyan Chen,
  • Zehui Zhao,
  • Xuanjun Wei,
  • Zhuomin Lyu,
  • Jing Li

摘要

Background

Diabetic wounds are characterized by impaired angiogenesis and disordered extracellular matrix remodeling, resulting in delayed repair. Bone marrow mesenchymal stem cells (BMSCs) promote wound healing mainly through paracrine mechanisms, but their function may be weakened in the diabetic microenvironment. Mechanical stimulation is an important biophysical cue that regulates stem cell behavior and secretion. This study investigated whether cyclic mechanical stretch enhances BMSC paracrine activity through a periostin (Postn)-associated Wnt/β-catenin pathway and improves diabetic wound healing.

Methods

BMSCs were subjected to cyclic stretch at 15% strain and 0.5 Hz for 10 h. Postn, Wnt/β-catenin pathway-related proteins, and paracrine factors, including VEGF, TGF-β1, and bFGF, were examined by qRT-PCR, Western blotting, and ELISA. si-Postn, XAV-939-mediated Wnt/β-catenin inhibition, and recombinant Postn rescue experiments were performed to clarify the underlying mechanism. Conditioned medium (CM) from different BMSC groups was used to treat rat umbilical vein endothelial cells and fibroblasts to assess migration and tube formation. The therapeutic effects of CM were further evaluated in a full-thickness diabetic rat wound model.

Results

Cyclic mechanical stretch increased BMSC spreading, altered F-actin organization, upregulated Postn expression, and promoted β-catenin nuclear accumulation. Mechanical stimulation also enhanced the expression of Wnt/β-catenin pathway-related proteins and increased the secretion of VEGF, TGF-β1, and bFGF. si-Postn attenuated Wnt/β-catenin activation and reduced the mechanically induced enhancement of paracrine factor secretion, whereas recombinant Postn supplementation partially restored these effects. Similarly, XAV-939-mediated inhibition of Wnt/β-catenin signaling suppressed the paracrine response of stretched BMSCs. Functionally, CM from mechanically stimulated BMSCs promoted endothelial cell migration, tube formation, and fibroblast migration in vitro, while these effects were weakened by Postn silencing or Wnt/β-catenin inhibition. In vivo, CM from stretched BMSCs accelerated diabetic wound repair, enhanced angiogenesis, and improved extracellular matrix organization and collagen maturation, whereas Postn silencing or Wnt/β-catenin inhibition reduced these therapeutic effects.

Conclusion

Cyclic mechanical stretch enhances the paracrine function of BMSCs through a Postn-associated Wnt/β-catenin signaling pathway. Conditioned medium derived from mechanically stimulated BMSCs promotes angiogenesis and matrix remodeling in diabetic wounds, suggesting a mechanobiology-based, cell-free therapeutic strategy for diabetic wound repair.