Raphanus sativus Linne Protects Human Nucleus Pulposus Cells against H2O2-Induced Damage by Inhibiting TREM2

Simple Summary: Intervertebral disc degeneration (IDD) occurs due to damage and loss of nucleus pulposus (NP) cells. This study investigated the protective effects of Raphanus sativus Linne (RSL), commonly known as radish, against oxidative stress caused by H2O2 in human NP cells and its ability to inhibit TREM2, a protein that induces apoptosis and degeneration in NP cells. RSL significantly improved cell survival by reducing the apoptosis markers cleaved caspase-3 and Bax and increasing Bcl2. It also enhanced mRNA levels of ACAN and Col2a1, important for NP cell function, and reduced levels of ADAMTS-4, ADAMTS-5, MMP3, and MMP13, which are involved in NP cell degeneration. Additionally, RSL downregulated TREM2 expression, which is elevated by H2O2 and causes disc degeneration. Overall, RSL extracts support human NP cells under oxidative stress and may help prevent IDD by regulating key degeneration pathways, particularly TREM2. Intervertebral disc degeneration (IDD) progresses owing to damage and depletion of nucleus pulposus (NP) cells. Cytoprotection mitigates oxidative stress, nutrient deprivation, and mechanical stress, which lead to cell damage and necrosis. We aimed to examine the protective effect of Raphanus sativus Linne (RSL), common radish, against oxidative stress by H2O2 in human NP cells and whether the RSL extracts can inhibit triggering receptor expressed on myeloid cells 2 (TREM2), an inducer of apoptosis and degeneration in NP cells. We administered hydrogen peroxide (H2O2) to cultured human NP cells treated with RSL extracts. We used immunoblotting and quantitative PCR to investigate expression of the apoptosis-associated proteins in cultured cells. RSL significantly enhanced cell survival by suppressing the activation of cleaved caspase-3 and Bax. In contrast, RSL extract increased Bcl2 concentration to downregulate apoptosis. Additionally, RSL treatment notably enhanced the mRNA levels of ACAN and Col2a1 while significantly reducing those of ADAMTS-4, ADAMTS-5, MMP3, and MMP13, key genes involved in NP degeneration. While H2O2 elevated TREM2 expression, causing disc degeneration, RSL downregulated TREM2 expression. Thus, our findings imply that RSL supports human NP cells under oxidative stress and regulates the pathways underlying disc degeneration, particularly TREM2, and that RSL extracts may potentially prevent IDD.