Department of Orthopedics, The Second Hospital of Lanzhou University, 82 Cuiying Men, Lanzhou, Gansu Province, 730030, China.
The Second Clinical Medical College, Lanzhou University, Lanzhou, China.
Mol Med. 2024 Jun 14;30(1):87. doi: 10.1186/s10020-024-00853-4.
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.
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.
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.
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.
椎间盘退变（IDD）是一种常见的肌肉骨骼退行性疾病，常导致腰痛，甚至残疾，丧失劳动能力，降低生活质量。尽管目前的研究取得了许多进展，但 IDD 的潜在机制仍不清楚。核髓核细胞（NPC）的凋亡是椎间盘退变（IDD）的重要病理机制。本研究评估了 S100A6 与 NPC 之间的关系及其潜在机制。
采用质谱、生物信息学和定量实时聚合酶链反应（qRT-PCR）分析筛选和验证不同退变程度人椎间盘标本中 IDD 的核心基因。采用 Western blot、免疫组化（IHC）和/或免疫荧光（IF）检测 S100A6 在人 NP 组织和 NPC 中的表达水平。采用流式细胞术、Western blot 和 IF 检测 NPC 凋亡表型和 Wnt/β-catenin 信号通路。在 NPC 中转染 S100A6 过表达或敲低载体，以确定其对细胞凋亡和 Wnt/β-catenin 信号通路活性的影响。此外，我们使用 XAV-939 抑制和 SKL2001 激活 Wnt/β-catenin 信号通路。还评估了 S100A6 抑制对 IDD 的治疗效果。
S100A6 在 IDD 中表达增加。体外，S100A6 表达增加促进了白细胞介素（IL）-1β诱导的 NPC 凋亡。相反，S100A6 表达的抑制部分缓解了纤维环（AF）穿刺诱导的大鼠 IDD 的进展。机制研究表明，S100A6 通过 Wnt/β-catenin 信号通路调节 NPC 凋亡。
本研究表明，S100A6 在 IDD 过程中表达增加，并通过调节 Wnt/β-catenin 信号通路促进 NPC 凋亡，提示 S100A6 是治疗 IDD 的一个有前途的新靶点。
