Effects of Hyperbaric Oxygen Intervention on the Degenerated Intervertebral Disc: From Molecular Mechanisms to Animal Models

MicroRNA (miRNA) 107 expression is downregulated but Wnt3a protein and β-catenin are upregulated in degenerated intervertebral disc (IVD). We investigated mir-107/Wnt3a-β-catenin signaling in vitro and in vivo following hyperbaric oxygen (HBO) intervention. Our results showed 96 miRNAs were upregula...

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Main Authors: Song-Shu Lin, Steve W. N. Ueng, Kowit-Yu Chong, Yi-Sheng Chan, Tsung-Ting Tsai, Li-Jen Yuan, Shih-Jung Liu, Chuen-Yung Yang, Hui-Yi Hsiao, Yi-Jen Hsueh, Chung-An Chen, Chi-Chien Niu
Format: Article
Language:English
Published: MDPI AG 2023-08-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/12/16/2111
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author Song-Shu Lin
Steve W. N. Ueng
Kowit-Yu Chong
Yi-Sheng Chan
Tsung-Ting Tsai
Li-Jen Yuan
Shih-Jung Liu
Chuen-Yung Yang
Hui-Yi Hsiao
Yi-Jen Hsueh
Chung-An Chen
Chi-Chien Niu
author_facet Song-Shu Lin
Steve W. N. Ueng
Kowit-Yu Chong
Yi-Sheng Chan
Tsung-Ting Tsai
Li-Jen Yuan
Shih-Jung Liu
Chuen-Yung Yang
Hui-Yi Hsiao
Yi-Jen Hsueh
Chung-An Chen
Chi-Chien Niu
author_sort Song-Shu Lin
collection DOAJ
description MicroRNA (miRNA) 107 expression is downregulated but Wnt3a protein and β-catenin are upregulated in degenerated intervertebral disc (IVD). We investigated mir-107/Wnt3a-β-catenin signaling in vitro and in vivo following hyperbaric oxygen (HBO) intervention. Our results showed 96 miRNAs were upregulated and 66 downregulated in degenerated nucleus pulposus cells (NPCs) following HBO treatment. The 3′ untranslated region (UTR) of the Wnt3a mRNA contained the “seed-matched-sequence” for miR-107. MiR-107 was upregulated and a marked suppression of Wnt3a was observed simultaneously in degenerated NPCs following HBO intervention. Knockdown of miR-107 upregulated Wnt3a expression in hyperoxic cells. HBO downregulated the protein expression of Wnt3a, phosphorylated LRP6, and cyclin D1. There was decreased TOP flash activity following HBO intervention, whereas the FOP flash activity was not affected. HBO decreased the nuclear translocation of β-catenin and decreased the secretion of MMP-3 and -9 in degenerated NPCs. Moreover, rabbit serum KS levels and the stained area for Wnt3a and β-catenin in repaired cartilage tended to be lower in the HBO group. We observed that HBO inhibits Wnt3a/β-catenin signaling-related pathways by upregulating miR-107 expression in degenerated NPCs. HBO may play a protective role against IVD degeneration and could be used as a future therapeutic treatment.
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spelling doaj.art-1571c142681e4d97be2e2f2c9081427a2023-11-19T00:37:42ZengMDPI AGCells2073-44092023-08-011216211110.3390/cells12162111Effects of Hyperbaric Oxygen Intervention on the Degenerated Intervertebral Disc: From Molecular Mechanisms to Animal ModelsSong-Shu Lin0Steve W. N. Ueng1Kowit-Yu Chong2Yi-Sheng Chan3Tsung-Ting Tsai4Li-Jen Yuan5Shih-Jung Liu6Chuen-Yung Yang7Hui-Yi Hsiao8Yi-Jen Hsueh9Chung-An Chen10Chi-Chien Niu11Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Taoyuan 333, TaiwanDepartment of Orthopaedic Surgery, Chang Gung Memorial Hospital, Taoyuan 333, TaiwanHyperbaric Oxygen Medical Research Laboratory, Bone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan 33305, TaiwanDepartment of Orthopaedic Surgery, Chang Gung Memorial Hospital, Taoyuan 333, TaiwanDepartment of Orthopaedic Surgery, Chang Gung Memorial Hospital, Taoyuan 333, TaiwanDepartment of Orthopaedic Surgery, E-Da Hospital, I-Shou University, Kaohsiung 82445, TaiwanDepartment of Mechanical Engineering, Chang Gung University, Taoyuan 333, TaiwanDepartment of Orthopaedic Surgery, Chang Gung Memorial Hospital, Taoyuan 333, TaiwanCenter for Tissue Engineering, Chang Gung Memorial Hospital, Taoyuan 333, TaiwanCenter for Tissue Engineering, Chang Gung Memorial Hospital, Taoyuan 333, TaiwanDepartment of Orthopaedic Surgery, Chang Gung Memorial Hospital, Taoyuan 333, TaiwanDepartment of Orthopaedic Surgery, Chang Gung Memorial Hospital, Taoyuan 333, TaiwanMicroRNA (miRNA) 107 expression is downregulated but Wnt3a protein and β-catenin are upregulated in degenerated intervertebral disc (IVD). We investigated mir-107/Wnt3a-β-catenin signaling in vitro and in vivo following hyperbaric oxygen (HBO) intervention. Our results showed 96 miRNAs were upregulated and 66 downregulated in degenerated nucleus pulposus cells (NPCs) following HBO treatment. The 3′ untranslated region (UTR) of the Wnt3a mRNA contained the “seed-matched-sequence” for miR-107. MiR-107 was upregulated and a marked suppression of Wnt3a was observed simultaneously in degenerated NPCs following HBO intervention. Knockdown of miR-107 upregulated Wnt3a expression in hyperoxic cells. HBO downregulated the protein expression of Wnt3a, phosphorylated LRP6, and cyclin D1. There was decreased TOP flash activity following HBO intervention, whereas the FOP flash activity was not affected. HBO decreased the nuclear translocation of β-catenin and decreased the secretion of MMP-3 and -9 in degenerated NPCs. Moreover, rabbit serum KS levels and the stained area for Wnt3a and β-catenin in repaired cartilage tended to be lower in the HBO group. We observed that HBO inhibits Wnt3a/β-catenin signaling-related pathways by upregulating miR-107 expression in degenerated NPCs. HBO may play a protective role against IVD degeneration and could be used as a future therapeutic treatment.https://www.mdpi.com/2073-4409/12/16/2111microRNAWnt3a/β-catenin signalingintervertebral discdegenerationhyperbaric oxygen
spellingShingle Song-Shu Lin
Steve W. N. Ueng
Kowit-Yu Chong
Yi-Sheng Chan
Tsung-Ting Tsai
Li-Jen Yuan
Shih-Jung Liu
Chuen-Yung Yang
Hui-Yi Hsiao
Yi-Jen Hsueh
Chung-An Chen
Chi-Chien Niu
Effects of Hyperbaric Oxygen Intervention on the Degenerated Intervertebral Disc: From Molecular Mechanisms to Animal Models
Cells
microRNA
Wnt3a/β-catenin signaling
intervertebral disc
degeneration
hyperbaric oxygen
title Effects of Hyperbaric Oxygen Intervention on the Degenerated Intervertebral Disc: From Molecular Mechanisms to Animal Models
title_full Effects of Hyperbaric Oxygen Intervention on the Degenerated Intervertebral Disc: From Molecular Mechanisms to Animal Models
title_fullStr Effects of Hyperbaric Oxygen Intervention on the Degenerated Intervertebral Disc: From Molecular Mechanisms to Animal Models
title_full_unstemmed Effects of Hyperbaric Oxygen Intervention on the Degenerated Intervertebral Disc: From Molecular Mechanisms to Animal Models
title_short Effects of Hyperbaric Oxygen Intervention on the Degenerated Intervertebral Disc: From Molecular Mechanisms to Animal Models
title_sort effects of hyperbaric oxygen intervention on the degenerated intervertebral disc from molecular mechanisms to animal models
topic microRNA
Wnt3a/β-catenin signaling
intervertebral disc
degeneration
hyperbaric oxygen
url https://www.mdpi.com/2073-4409/12/16/2111
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