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用于研究局部骨重塑调控的小梁骨类器官模型。

Trabecular bone organoid model for studying the regulation of localized bone remodeling.

机构信息

Department of Chemical Engineering, Institute for Applied Life Sciences, University of Massachusetts, Amherst, MA 01003, USA.

Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, MA 01003, USA.

出版信息

Sci Adv. 2021 Jan 20;7(4). doi: 10.1126/sciadv.abd6495. Print 2021 Jan.

DOI:10.1126/sciadv.abd6495
PMID:33523925
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7817107/
Abstract

Trabecular bone maintains physiological homeostasis and consistent structure and mass through repeated cycles of bone remodeling by means of tightly localized regulation. The molecular and cellular processes that regulate localized bone remodeling are poorly understood because of a lack of relevant experimental models. A tissue-engineered model is described here that reproduces bone tissue complexity and bone remodeling processes with high fidelity and control. An osteoid-inspired biomaterial-demineralized bone paper-directs osteoblasts to deposit structural mineralized bone tissue and subsequently acquire the resting-state bone lining cell phenotype. These cells activate and shift their secretory profile to induce osteoclastogenesis in response to chemical stimulation. Quantitative spatial mapping of cellular activities in resting and activated bone surface coculture showed that the resting-state bone lining cell network actively directs localized bone remodeling by means of paracrine signaling and cell-to-cell contact. This model may facilitate further investigation of trabecular bone niche biology.

摘要

小梁骨通过局部紧密调控的骨重建反复周期来维持生理稳态和一致的结构和质量。由于缺乏相关的实验模型,因此对于调控局部骨重建的分子和细胞过程知之甚少。本文描述了一种组织工程模型,该模型能够以高精度和可控性再现骨组织的复杂性和骨重建过程。一种类骨诱导的生物材料-脱矿骨纸-指导成骨细胞沉积结构性矿化骨组织,随后获得静止状态的骨衬细胞表型。这些细胞被激活并改变其分泌特征,以响应化学刺激诱导破骨细胞生成。静止和激活的骨表面共培养的细胞活性的定量空间映射表明,静止状态的骨衬细胞网络通过旁分泌信号和细胞-细胞接触积极地指导局部骨重建。该模型可能有助于进一步研究小梁骨龛生物学。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8cb/7817107/c91c3f33852f/abd6495-F2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8cb/7817107/c91c3f33852f/abd6495-F2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8cb/7817107/c91c3f33852f/abd6495-F2.jpg

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