Mechanical stimulation activates Postn-mediated Wnt/β-catenin pathway to enhance BMSCs paracrine function and promote wound healing in diabetic rats.
- 1Department of Burns and Plastic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.
- 2Department of Burns and Plastic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China. [email protected].
- 3Department of Burns and Plastic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China. [email protected].
Abstract
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.
Related
- Topical application of urolithin A activates mitophagy and enhances mitochondrial function to promote skin longevity
- Nano-NucleOTAC-mediated Z-DNA transformation disrupts mycobacterium tuberculosis biofilms and activates antibacterial immunity.
- In vivo evaluation of noninvasive temporal interference stimulation for tibial nerve-mediated bladder reflex modulation in rats
- Low-frequency passive mechanical stimulation produces antidepressant-like effects in rats involving gut–brain axis modulation
- Trajectories of cardiopulmonary adaptation and executive function in elite endurance athletes receiving transcranial direct current stimulation with interval training
BibTeX
@article{zhang2026mechanical,
title = {{Mechanical stimulation activates Postn-mediated Wnt/β-catenin pathway to enhance BMSCs paracrine function and promote wound healing in diabetic rats.}},
author = {Dong Zhang and Haowei Zhou and Congying Zhao and Zhanjun Lei and Zhe Liu and Junwei Su and Gaoyan Chen and Zehui Zhao and Xuanjun Wei and Zhuomin Lyu and Jing Li},
journal = {Stem cell research \& therapy},
year = {2026},
month = jul,
doi = {10.1186/s13287-026-05197-w},
url = {https://europepmc.org/article/MED/42972600},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Mechanical stimulation activates Postn-mediated Wnt/β-catenin pathway to enhance BMSCs paracrine function and promote wound healing in diabetic rats.
AU - Dong Zhang
AU - Haowei Zhou
AU - Congying Zhao
AU - Zhanjun Lei
AU - Zhe Liu
AU - Junwei Su
AU - Gaoyan Chen
AU - Zehui Zhao
AU - Xuanjun Wei
AU - Zhuomin Lyu
AU - Jing Li
PY - 2026
DA - 2026/07/31
JO - Stem cell research & therapy
DO - 10.1186/s13287-026-05197-w
UR - https://europepmc.org/article/MED/42972600
AB - 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.
SN - 1757-6512
ER -