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载 MY-1 的纳米羟基磷灰石通过 HSP47 依赖的机制增加早期细胞外基质中 III 型胶原蛋白的沉积,从而加速骨再生。

MY-1-Loaded Nano-Hydroxyapatite Accelerated Bone Regeneration by Increasing Type III Collagen Deposition in Early-Stage ECM via a Hsp47-Dependent Mechanism.

机构信息

Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, P. R. China.

Department of Orthopedics - Spinal Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, P. R. China.

出版信息

Adv Healthc Mater. 2023 Aug;12(20):e2300332. doi: 10.1002/adhm.202300332. Epub 2023 Apr 20.

Abstract

The extracellular matrix (ECM) plays a crucial part in regulating stem cell function through its distinctive mechanical and chemical effect. Therefore, it is worth studying how to activate the driving force of osteoblast cells by dynamic changing of ECM and accelerate the bone regeneration. In this research, a novel peptide MY-1 is designed and synthesized. To achieve its sustained releasing, the nano-hydroxyapatite (nHA) is chosen as the carrier of MY-1 by mixed adsorption. The results reveal that the sustainable releasing of MY-1 regulates the synthesis and secretion of ECM from rat bone marrow mesenchymal stem cells (rBMSCs), which promotes the cell migration and osteogenic differentiation in the early stage of bone regeneration. Further analyses demonstrate that MY-1 increases the expression and nuclear translocation of β-catenin, and then upregulates the level of heat shock protein 47 (Hsp47), thereby accelerating the synthesis and secretion of type III collagen (Col III) at the early stage. Finally, the promoted rapid transformation of Col III to Col I at late stage benefits the bone regeneration. Hence, this study can provide a theoretical basis for the local application of MY-1 in bone regeneration.

摘要

细胞外基质 (ECM) 通过其独特的机械和化学效应在调节干细胞功能方面起着至关重要的作用。因此,值得研究如何通过 ECM 的动态变化激活成骨细胞的驱动力,从而加速骨再生。在这项研究中,设计并合成了一种新型肽 MY-1。为了实现其持续释放,选择纳米羟基磷灰石 (nHA) 作为 MY-1 的载体通过混合吸附。结果表明,MY-1 的持续释放调节了大鼠骨髓间充质干细胞(rBMSCs)中 ECM 的合成和分泌,从而促进了骨再生早期细胞的迁移和成骨分化。进一步的分析表明,MY-1 增加了 β-连环蛋白的表达和核易位,进而上调了热休克蛋白 47(Hsp47)的水平,从而加速了早期 III 型胶原(Col III)的合成和分泌。最后,晚期促进 Col III 快速转化为 Col I 有利于骨再生。因此,本研究可为 MY-1 在骨再生中的局部应用提供理论依据。

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