Stigmasterol alleviates endplate chondrocyte degeneration through inducing mitophagy by enhancing PINK1 mRNA acetylation via the ESR1/NAT10 axis
Hao Li, Xiaofeng Chen, Baoci Huang, Junjie He, Junxian Xie, Weijun Guo, Jinjun Liang, Jiajian Ruan, Jincheng Liu, Zhen Xiang, Lixin Zhu
TL;DR
Stigmasterol helps prevent spinal disc degeneration by triggering a cellular cleanup process in cartilage cells.
Contribution
Stigmasterol's novel mechanism via ESR1/NAT10 axis and PINK1 mRNA acetylation is revealed for the first time.
Findings
Stigmasterol alleviates endplate chondrocyte degeneration by inducing mitophagy.
NAT10 enhances PINK1 expression through mRNA acetylation in chondrocytes.
Stigmasterol regulates NAT10 via estrogen receptor 1 in degenerated cells.
Abstract
Intervertebral disc degeneration (IVDD) is a core factor in spinal degeneration. To date, there is no effective treatment for IVDD. It is urgent to identify the pathogenesis of IVDD to develop effective strategies for IVDD treatment. Alleviating endplate chondrocyte degeneration is a promising strategy for IVDD treatment, while mitophagy prevents degeneration of endplate chondrocytes. Stigmasterol (STM) protects neurons from injuries by triggering mitophagy, yet the effect of STM on the mitophagy of endplate chondrocytes in IVDD has not been reported. In this study, endplate chondrocyte degeneration was induced by interleukin-1β, and the ribonucleic acid (RNA) acetylation level was identified by acetylated RNA immunoprecipitation. Herein, results indicated that STM alleviated endplate chondrocyte degeneration. Besides, STM induced PTEN-induced kinase 1 (PINK1)-mediated mitophagy in…
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Taxonomy
TopicsOsteoarthritis Treatment and Mechanisms · Cancer-related molecular mechanisms research · RNA Interference and Gene Delivery