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...
Main Authors: | , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2023-08-01
|
Series: | Cells |
Subjects: | |
Online Access: | https://www.mdpi.com/2073-4409/12/16/2111 |
_version_ | 1797585159883587584 |
---|---|
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. |
first_indexed | 2024-03-11T00:01:57Z |
format | Article |
id | doaj.art-1571c142681e4d97be2e2f2c9081427a |
institution | Directory Open Access Journal |
issn | 2073-4409 |
language | English |
last_indexed | 2024-03-11T00:01:57Z |
publishDate | 2023-08-01 |
publisher | MDPI AG |
record_format | Article |
series | Cells |
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 |
work_keys_str_mv | AT songshulin effectsofhyperbaricoxygeninterventiononthedegeneratedintervertebraldiscfrommolecularmechanismstoanimalmodels AT stevewnueng effectsofhyperbaricoxygeninterventiononthedegeneratedintervertebraldiscfrommolecularmechanismstoanimalmodels AT kowityuchong effectsofhyperbaricoxygeninterventiononthedegeneratedintervertebraldiscfrommolecularmechanismstoanimalmodels AT yishengchan effectsofhyperbaricoxygeninterventiononthedegeneratedintervertebraldiscfrommolecularmechanismstoanimalmodels AT tsungtingtsai effectsofhyperbaricoxygeninterventiononthedegeneratedintervertebraldiscfrommolecularmechanismstoanimalmodels AT lijenyuan effectsofhyperbaricoxygeninterventiononthedegeneratedintervertebraldiscfrommolecularmechanismstoanimalmodels AT shihjungliu effectsofhyperbaricoxygeninterventiononthedegeneratedintervertebraldiscfrommolecularmechanismstoanimalmodels AT chuenyungyang effectsofhyperbaricoxygeninterventiononthedegeneratedintervertebraldiscfrommolecularmechanismstoanimalmodels AT huiyihsiao effectsofhyperbaricoxygeninterventiononthedegeneratedintervertebraldiscfrommolecularmechanismstoanimalmodels AT yijenhsueh effectsofhyperbaricoxygeninterventiononthedegeneratedintervertebraldiscfrommolecularmechanismstoanimalmodels AT chunganchen effectsofhyperbaricoxygeninterventiononthedegeneratedintervertebraldiscfrommolecularmechanismstoanimalmodels AT chichienniu effectsofhyperbaricoxygeninterventiononthedegeneratedintervertebraldiscfrommolecularmechanismstoanimalmodels |