Kartogenin-mediated transformation of osteo-chondroprogenitors from stem cells facilitates bone repair via intramembranous and endochondral ossification

IF 14.2 1区 材料科学 Q1 ENGINEERING, MULTIDISCIPLINARY Composites Part B: Engineering Pub Date : 2025-01-21 DOI:10.1016/j.compositesb.2025.112161
Chengyuan Liu , Huan Wang , Ye Gu , Zhangqin Yuan , Qifan Yu , Changjiang Liu , Han Sun , Yuanchen Zhu , Qianping Guo , Caihong Zhu , Bin Li
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Abstract

Bone tissue engineering through regulation of mesenchymal stem cells (MSCs) provides a promising strategy for bone repair via intramembranous or endochondral ossification. Here, the novel approach of promoting the transformation of MSCs into osteo-chondroprogenitors to simulate the initial process in bone development to improve bone repair was proposed and validated via the use of a small-molecule drug, kartogenin (KGN). The transformation of MSCs into osteo-chondroprogenitors was effectively achieved by KGN treatment in 1 week. In the Ca2+-rich bone microenvironment in vitro, the transformation of MSCs markedly enhanced osteoblast generation by upregulating SOX9, RUNX2, and β-catenin. In vivo experiments further verified that the transformation of osteo-chondroprogenitors drove rapid bone repair within 4 weeks, through both intramembranous and endochondral ossification. This study proposes accelerating bone regeneration by inducing the transformation of MSCs into osteo-chondroprogenitors and reveals the co-existence of intramembranous and endochondral ossification during bone repair, providing new insights for bone regeneration.
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kartogenin介导的骨软骨祖细胞从干细胞转化,通过膜内和软骨内成骨促进骨修复
通过调节间充质干细胞(MSCs)进行骨组织工程为通过膜内或软骨内成骨进行骨修复提供了一种有前景的策略。本文提出了一种促进间充质干细胞向骨软骨祖细胞转化的新方法,以模拟骨发育的初始过程,从而改善骨修复,并通过使用小分子药物kartogenin (KGN)进行了验证。KGN在1周内有效地实现了MSCs向骨软骨祖细胞的转化。在体外富含Ca2+的骨微环境中,MSCs的转化通过上调SOX9、RUNX2和β-catenin显著增强成骨细胞的生成。体内实验进一步证实骨-软骨祖细胞的转化在4周内通过膜内和软骨内成骨驱动骨快速修复。本研究提出通过诱导MSCs向骨软骨祖细胞转化来加速骨再生,揭示了骨修复过程中膜内成骨和软骨内成骨并存,为骨再生提供了新的见解。
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来源期刊
Composites Part B: Engineering
Composites Part B: Engineering 工程技术-材料科学:复合
CiteScore
24.40
自引率
11.50%
发文量
784
审稿时长
21 days
期刊介绍: Composites Part B: Engineering is a journal that publishes impactful research of high quality on composite materials. This research is supported by fundamental mechanics and materials science and engineering approaches. The targeted research can cover a wide range of length scales, ranging from nano to micro and meso, and even to the full product and structure level. The journal specifically focuses on engineering applications that involve high performance composites. These applications can range from low volume and high cost to high volume and low cost composite development. The main goal of the journal is to provide a platform for the prompt publication of original and high quality research. The emphasis is on design, development, modeling, validation, and manufacturing of engineering details and concepts. The journal welcomes both basic research papers and proposals for review articles. Authors are encouraged to address challenges across various application areas. These areas include, but are not limited to, aerospace, automotive, and other surface transportation. The journal also covers energy-related applications, with a focus on renewable energy. Other application areas include infrastructure, off-shore and maritime projects, health care technology, and recreational products.
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