4.8 Article

Synthetic presentation of noncanonical Wnt5a motif promotes mechanosensing-dependent differentiation of stem cells and regeneration

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SCIENCE ADVANCES
卷 5, 期 10, 页码 -

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AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.aaw3896

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资金

  1. National Natural Science Foundation of China [31570979]
  2. General Research Fund grant from the Research Grants Council of Hong Kong [14202215, 14220716]
  3. Shun Hing Institute of Advanced Engineering (The Chinese University of Hong Kong) [BME-p3-15]
  4. Health and Medical Research Fund
  5. Food and Health Bureau
  6. Government of the Hong Kong Special Administrative Region [04152836]
  7. Chow Yuk Ho Technology Centre for Innovative Medicine (The Chinese University of Hong Kong)
  8. Hong Kong Research Grants Council Theme-based Research Scheme [T13-402/17-N]

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Noncanonical Wnt signaling in stem cells is essential to numerous developmental events. However, no prior studies have capitalized on the osteoinductive potential of noncanonical Wnt ligands to functionalize biomaterials in enhancing the osteogenesis and associated skeleton formation. Here, we investigated the efficacy of the function-alization of biomaterials with a synthetic Wnt5a mimetic ligand (Foxy5 peptide) to promote the mechanosensing and osteogenesis of human mesenchymal stem cells by activating noncanonical Wnt signaling. Our findings showed that the immobilized Wnt5a mimetic ligand activated noncanonical Wnt signaling via the up-regulation of Disheveled 2 and downstream RhoA-ROCK signaling, leading to enhanced intracellular calcium level, F-actin stability, actomyosin contractility, and cell adhesion structure development.This enhanced mechanotransduction in stem cells promoted the in vitro osteogenic lineage commitment and the in vivo healing of rat calvarial defects. Our work provides valuable guidance for the developmentally inspired design of biomaterials for a wide array of therapeutic applications.

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