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POSTN 通过激活 Wnt/β-catenin 和 NF-κB 信号通路促进椎间盘退变中髓核细胞衰老和细胞外基质代谢。

POSTN promotes nucleus pulposus cell senescence and extracellular matrix metabolism via activing Wnt/β-catenin and NF-κB signal pathway in intervertebral disc degeneration.

机构信息

Lanzhou University Second Hospital, 82 Cuiyingmen, Lanzhou 730030, PR China; Orthopaedics Key Laboratory of Gansu Province, Lanzhou 730030, PR China.

The 947th Hospital of the People's Liberation Army Ground Force of Xinjiang Uygur Autonomous Region, Kashgar, PR China.

出版信息

Cell Signal. 2024 Sep;121:111277. doi: 10.1016/j.cellsig.2024.111277. Epub 2024 Jun 27.

DOI:10.1016/j.cellsig.2024.111277
PMID:38944256
Abstract

BACKGROUND

Intervertebral disc (IVD) degeneration (IVDD) is a prevalent condition contributing to back pain and disability. Periostin (POSTN) has emerged as a potential molecular marker and therapeutic target in IVDD, prompting further investigation into its role and mechanisms.

METHODS

This study employs bioinformatics analysis combined with experimental validation to explore the role of POSTN in IVDD. Gene expression datasets from the GEO database were analyzed to identify genes associated with IVDD, and the effects of POSTN on rat nucleus pulposus (NP) cells senescence and extracellular matrix (ECM) metabolism were assessed both in vitro and in vivo.

RESULTS

Elevated POSTN expression was observed in degenerated discs from IVDD patients, correlating with disease severity. In vitro experiments demonstrated that POSTN promotes NP cells senescence and ECM metabolism in a dose- and time-dependent manner. In vivo studies confirmed that POSTN inhibition can ameliorate the progression of IVDD. Further mechanistic insights revealed that POSTN may exert its effects by activating the NF-κB and Wnt/β-catenin signaling pathways.

CONCLUSION

POSTN plays a significant role in the pathogenesis of IVDD, with its upregulated expression closely linked to NP cells senescence and ECM metabolism. Targeting POSTN could offer a novel therapeutic strategy for IVDD. Additionally, the study predicts small molecules that may inhibit POSTN expression, providing potential candidates for the development of new drug treatments.

摘要

背景

椎间盘退变(IVDD)是一种常见的病症,会导致腰痛和残疾。外泌体(POSTN)已成为 IVDD 潜在的分子标志物和治疗靶点,促使人们进一步研究其作用和机制。

方法

本研究采用生物信息学分析结合实验验证,探讨 POSTN 在 IVDD 中的作用。对 GEO 数据库中的基因表达数据集进行分析,以确定与 IVDD 相关的基因,并在体外和体内评估 POSTN 对大鼠髓核(NP)细胞衰老和细胞外基质(ECM)代谢的影响。

结果

在 IVDD 患者退变的椎间盘组织中观察到 POSTN 表达升高,与疾病严重程度相关。体外实验表明,POSTN 以剂量和时间依赖的方式促进 NP 细胞衰老和 ECM 代谢。体内研究证实,POSTN 抑制可改善 IVDD 的进展。进一步的机制研究表明,POSTN 可能通过激活 NF-κB 和 Wnt/β-catenin 信号通路发挥作用。

结论

POSTN 在 IVDD 的发病机制中起着重要作用,其上调表达与 NP 细胞衰老和 ECM 代谢密切相关。针对 POSTN 可能为 IVDD 提供一种新的治疗策略。此外,该研究预测了可能抑制 POSTN 表达的小分子,为开发新的药物治疗提供了潜在的候选药物。

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