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

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

doi:10.3390/cells12162111

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

Cells. 2023 Aug 21;12(16):2111. doi: 10.3390/cells12162111.

Authors

Song-Shu Lin^{1

2

3}, Steve W N Ueng^{1

3

4}, Kowit-Yu Chong^{3

5}, Yi-Sheng Chan^{1

3}, Tsung-Ting Tsai^{1

3}, Li-Jen Yuan⁶, Shih-Jung Liu⁷, Chuen-Yung Yang^{1

3}, Hui-Yi Hsiao^{8

9}, Yi-Jen Hsueh^{8

10}, Chung-An Chen^{1

3}, Chi-Chien Niu^{1

3

4}

Affiliations

¹ Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan.
² Department of Nursing, Chang Gung University of Science and Technology, Taoyuan 33302, Taiwan.
³ Hyperbaric Oxygen Medical Research Laboratory, Bone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan.
⁴ College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
⁵ Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
⁶ Department of Orthopaedic Surgery, E-Da Hospital, I-Shou University, Kaohsiung 82445, Taiwan.
⁷ Department of Mechanical Engineering, Chang Gung University, Taoyuan 333, Taiwan.
⁸ Center for Tissue Engineering, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan.
⁹ Department of Biomedical Science, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
¹⁰ Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan.

Abstract

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.

Keywords: Wnt3a/β-catenin signaling; degeneration; hyperbaric oxygen; intervertebral disc; microRNA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3' Untranslated Regions
Animals
Hyperbaric Oxygenation*
MicroRNAs* / genetics
Models, Animal
Nucleus Pulposus*
Oxygen
Rabbits
beta Catenin

Substances

beta Catenin
Oxygen
3' Untranslated Regions
MicroRNAs

Grants and funding

This research was supported in part by grants from the National Science Council (112-2314-B-182-059, 112-2314-B-182A-144) and Chang Gung Memorial Hospital, Taiwan, Republic of China (CRRPG3K0061~3).