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非典型 Wnt5a 基序的合成呈现促进了干细胞的机械感知依赖性分化和再生。

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

机构信息

Department of Biomedical Engineering, The Chinese University of Hong Kong, Sha Tin, New Territories 999077, Hong Kong, P. R. China.

Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, New Territories 999077, Hong Kong, P. R. China.

出版信息

Sci Adv. 2019 Oct 16;5(10):eaaw3896. doi: 10.1126/sciadv.aaw3896. eCollection 2019 Oct.

DOI:10.1126/sciadv.aaw3896
PMID:31663014
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6795506/
Abstract

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 functionalization 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.

摘要

非经典 Wnt 信号在干细胞中对于许多发育事件至关重要。然而，以前的研究尚未利用非经典 Wnt 配体的成骨潜能来功能化生物材料，以增强成骨作用和相关骨骼形成。在这里，我们研究了用合成的 Wnt5a 模拟配体（Foxy5 肽）功能化生物材料的功效，通过激活非经典 Wnt 信号来促进人骨髓间充质干细胞的机械感知和成骨作用。我们的研究结果表明，固定化的 Wnt5a 模拟配体通过上调 Disheveled 2 和下游 RhoA-ROCK 信号激活非经典 Wnt 信号，导致细胞内钙离子水平、F-肌动蛋白稳定性、肌球蛋白收缩力和细胞黏附结构的发展增强。这种增强的干细胞力学转导促进了体外成骨谱系的分化和体内大鼠颅骨缺损的愈合。我们的工作为广泛治疗应用的生物材料的发育启发式设计提供了有价值的指导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49d3/6795506/1695e0e1b938/aaw3896-F6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49d3/6795506/397d66f37d2e/aaw3896-F1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49d3/6795506/b4923944077b/aaw3896-F3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49d3/6795506/9e3e213a6775/aaw3896-F4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49d3/6795506/5de99f281325/aaw3896-F5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49d3/6795506/1695e0e1b938/aaw3896-F6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49d3/6795506/397d66f37d2e/aaw3896-F1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49d3/6795506/0b265b493ad1/aaw3896-F2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49d3/6795506/b4923944077b/aaw3896-F3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49d3/6795506/9e3e213a6775/aaw3896-F4.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49d3/6795506/1695e0e1b938/aaw3896-F6.jpg

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