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

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.

Hyperbaric oxygen therapy for the treatment of hypoxic/ischemic injury upon perinatal asphyxia—are we there yet?

“…The exposure of nucleus pulposus cells to HBOT (100% oxygen at 2.5 ATA) upregulated mir-107. This microRNA not only inhibits its direct target Wnt3a ( 60 ) but also suppresses the HMGB1/RAGE/NF-κB pathway, thus deactivating metalloproteases (MMP-3 and MMP-9), calcium-dependent zinc-containing endopeptidases that contribute to the disruption of the blood–brain barrier and extracellular matrix ( 61 ). Mir-107 was downregulated in UCB of human patients suffering from HI ( 56 ), as well as downregulated in blood and upregulated in the brains of rats subjected to transient focal cerebral ischemia ( 48 ); however, other studies found the opposite direction of changes ( 62 , 63 ).…”

From drugs to biomaterials: a review of emerging therapeutic strategies for intervertebral disc inflammation

“…The causes of IDD are diverse, encompassing genetics; biomechanical changes; alterations in the cellular microenvironment; bacterial or microbial infections; and lifestyle factors such as smoking, alcohol consumption, and obesity. Throughout the IDD process, an increase in pro-inflammatory cytokines within IVD cells is observed, culminating in cell degeneration and necrosis, ultimately leading to ECM degradation ( Roughley, 2004 ; Adams et al., 2009 ; Kepler et al., 2013 ; Lin et al., 2023 ). This, in turn, brings about alterations in the structure and biomechanical properties of the spine.…”