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非经典 Wnt 信号参与 Jagged1 诱导的人牙髓干细胞成骨/成牙分化。

Non-canonical Wnt signaling participates in Jagged1-induced osteo/odontogenic differentiation in human dental pulp stem cells.

机构信息

Dental Stem Cell Biology Research Unit, Faculty of Dentistry, Chulalongkorn University, 34 Henri-Dunant Rd. Pathumwan, Bangkok, 10330, Thailand.

Department of Pathology, Faculty of Veterinary Science, Chulalongkorn University, 39 Henri-Dunant Rd. Pathumwan, Bangkok, Bangkok, 10330, Thailand.

出版信息

Sci Rep. 2022 May 9;12(1):7583. doi: 10.1038/s41598-022-11596-9.

DOI:10.1038/s41598-022-11596-9
PMID:35534526
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9085777/
Abstract

Osteoblast differentiation requires the interaction of various cell signaling pathways to modulate cell responses. Notch and Wnt signaling are among the crucial pathways that control numerous biological processes, including osteo/odontogenic differentiation. The aim of the present study was to examine the involvement of Wnt signaling in the Jagged1-induced osteo/odontogenic differentiation in human dental pulp stem cells (hDPSCs). The Wnt-related gene expression was analyzed from publicly available data of Jagged1-treated human dental pulp cells. The mRNA expression of Wnt ligands (WNT2B, WNT5A, WNT5B, and WNT16) and Wnt inhibitors (DKK1, DKK2, and SOST) were confirmed using real-time polymerase chain reaction. Among the Wnt ligands, WNT2B and WNT5A mRNA levels were upregulated after Jagged1 treatment. In contrast, the Wnt inhibitors DKK1, DKK2, and SOST mRNA levels were downregulated. Recombinant WNT5A, but not WNT2B, significantly promoted in vitro mineral deposition by hDPSCs. Wnt signaling inhibition using IWP-2, but not DKK1, inhibited Jagged1-induced alkaline phosphatase (ALP) activity, mineralization, and osteo/odontogenic marker gene expression in hDPSCs. In conclusion, Jagged1 promoted hDPSC osteo/odontogenic differentiation by modulating the non-canonical Wnt pathway.

摘要

成骨细胞分化需要各种细胞信号通路的相互作用来调节细胞反应。Notch 和 Wnt 信号通路是控制包括骨/牙源性分化在内的许多生物学过程的关键通路之一。本研究旨在探讨 Wnt 信号通路在 Jagged1 诱导的人牙髓干细胞（hDPSCs）成骨/牙源性分化中的作用。分析了 Jagged1 处理的人牙髓细胞的公开数据中与 Wnt 相关的基因表达。使用实时聚合酶链反应（PCR）证实了 Wnt 配体（WNT2B、WNT5A、WNT5B 和 WNT16）和 Wnt 抑制剂（DKK1、DKK2 和 SOST）的 mRNA 表达。在 Wnt 配体中，Jagged1 处理后 WNT2B 和 WNT5A 的 mRNA 水平上调。相比之下，Wnt 抑制剂 DKK1、DKK2 和 SOST 的 mRNA 水平下调。重组 WNT5A 而非 WNT2B 显著促进 hDPSCs 的体外矿化沉积。Wnt 信号通路抑制剂 IWP-2 而非 DKK1 抑制 Jagged1 诱导的 hDPSCs 碱性磷酸酶（ALP）活性、矿化和骨/牙源性标记基因表达。总之，Jagged1 通过调节非经典 Wnt 通路促进 hDPSC 成骨/牙源性分化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33e1/9085777/1be119bd3fc5/41598_2022_11596_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33e1/9085777/5d36183f3634/41598_2022_11596_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33e1/9085777/dfa239b6b1ee/41598_2022_11596_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33e1/9085777/ab96192ce14a/41598_2022_11596_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33e1/9085777/1b3e4616255e/41598_2022_11596_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33e1/9085777/9449448b340c/41598_2022_11596_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33e1/9085777/1be119bd3fc5/41598_2022_11596_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33e1/9085777/5d36183f3634/41598_2022_11596_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33e1/9085777/dfa239b6b1ee/41598_2022_11596_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33e1/9085777/ab96192ce14a/41598_2022_11596_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33e1/9085777/1b3e4616255e/41598_2022_11596_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33e1/9085777/9449448b340c/41598_2022_11596_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33e1/9085777/1be119bd3fc5/41598_2022_11596_Fig6_HTML.jpg

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