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人牙髓干细胞衍生细胞外基质通过 Hippo 和 Wnt 通路促进矿化。

Human dental pulp stem cells derived extracellular matrix promotes mineralization via Hippo and Wnt pathways.

机构信息

Center of Excellence for Dental Stem Cell Biology and Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, 34 Henri-Dunant Rd. Pathumwan, Bangkok, 10330, Thailand.

Centre de Recherche des Cordeliers, Université Paris Cité, Sorbonne Université, INSERM UMR1138, Molecular Oral Pathophysiology, 75006, Paris, France.

出版信息

Sci Rep. 2024 Mar 21;14(1):6777. doi: 10.1038/s41598-024-56845-1.

Abstract

Extracellular matrix (ECM) is an intricate structure providing the microenvironment niche that influences stem cell differentiation. This study aimed to investigate the efficacy of decellularized ECM derived from human dental pulp stem cells (dECM_DPSCs) and gingival-derived mesenchymal stem cells (dECM_GSCs) as an inductive scaffold for osteogenic differentiation of GSCs. The proteomic analysis demonstrated that common and signature matrisome proteins from dECM_DPSCs and dECM_GSCs were related to osteogenesis/osteogenic differentiation. RNA sequencing data from GSCs reseeded on dECM_DPSCs revealed that dECM_DPSCs upregulated genes related to the Hippo and Wnt signaling pathways in GSCs. In the inhibitor experiments, results revealed that dECM_DPSCs superiorly promoted GSCs osteogenic differentiation, mainly mediated through Hippo and Wnt signaling. The present study emphasizes the promising translational application of dECM_DPSCs as a bio-scaffold rich in favorable regenerative microenvironment for tissue engineering.

摘要

细胞外基质 (ECM) 是一种复杂的结构,提供影响干细胞分化的微环境小生境。本研究旨在探讨人牙髓干细胞 (dECM_DPSCs) 和牙龈来源间充质干细胞 (dECM_GSCs) 的脱细胞 ECM 作为诱导 GSCs 成骨分化的诱导支架的功效。蛋白质组学分析表明,来自 dECM_DPSCs 和 dECM_GSCs 的常见和特征性基质蛋白与成骨/成骨分化有关。在重新接种到 dECM_DPSCs 上的 GSCs 的 RNA 测序数据中,发现 dECM_DPSCs 上调了与 GSCs 中的 Hippo 和 Wnt 信号通路相关的基因。在抑制剂实验中,结果表明 dECM_DPSCs 可通过 Hippo 和 Wnt 信号通路促进 GSCs 成骨分化。本研究强调了 dECM_DPSCs 作为富含有利再生微环境的生物支架在组织工程中的有前途的转化应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5d3/10957957/20c150455755/41598_2024_56845_Fig1_HTML.jpg

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