Molecular Medicine (Jun 2024)

S100A6 Regulates nucleus pulposus cell apoptosis via Wnt/β-catenin signaling pathway: an in vitro and in vivo study

  • Fengguang Yang,
  • Yanni Duan,
  • Yanhu Li,
  • Daxue Zhu,
  • Zhaoheng Wang,
  • Zhangbin Luo,
  • Yizhi Zhang,
  • Guangzhi Zhang,
  • Xuegang He,
  • Xuewen Kang

DOI
https://doi.org/10.1186/s10020-024-00853-4
Journal volume & issue
Vol. 30, no. 1
pp. 1 – 18

Abstract

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Abstract Background Intervertebral disc degeneration (IDD) is a common musculoskeletal degenerative disease, which often leads to low back pain and even disability, resulting in loss of labor ability and decreased quality of life. Although many progresses have been made in the current research, the underlying mechanism of IDD remains unclear. The apoptosis of nucleus pulposus (NP) cells (NPCs) is an important pathological mechanism in intervertebral disc degeneration (IDD). This study evaluated the relationship between S100A6 and NPCs and its underlying mechanism. Methods Mass spectrometry, bioinformatics, and quantitative real-time polymerase chain reaction (qRT-PCR) analyses were used to screen and verify hub genes for IDD in human IVD specimens with different degeneration degrees. Western blotting, immunohistochemistry (IHC), and/or immunofluorescence (IF) were used to detect the expression level of S100A6 in human NP tissues and NPCs. The apoptotic phenotype of NPCs and Wnt/β-catenin signaling pathway were evaluated using flow cytometry, western blotting, and IF. S100A6 was overexpressed or knocked down in NPCs to determine its impact on apoptosis and Wnt/β-catenin signaling pathway activity. Moreover, we used the XAV-939 to inhibit and SKL2001 to activate the Wnt/β-catenin signaling pathway. The therapeutic effect of S100A6 inhibition on IDD was also evaluated. Results S100A6 expression increased in IDD. In vitro, increased S100A6 expression promoted apoptosis in interleukin (IL)-1β-induced NPCs. In contrast, the inhibition of S100A6 expression partially alleviated the progression of annulus fibrosus (AF) puncture-induced IDD in rats. Mechanistic studies revealed that S100A6 regulates NPC apoptosis via Wnt/β-catenin signaling pathway. Conclusions This study showed that S100A6 expression increased during IDD and promoted NPCs apoptosis by regulating the Wnt/β-catenin signaling pathway, suggesting that S100A6 is a promising new therapeutic target for IDD.

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