LncRNA AC006064.4-201 serves as a novel molecular marker in alleviating cartilage senescence and protecting against osteoarthritis by destabilizing CDKN1B mRNA via interacting with PTBP1.
LncRNA AC006064.4-201 serves as a novel molecular marker in alleviating cartilage senescence and protecting against osteoarthritis by destabilizing CDKN1B mRNA via interacting with PTBP1.
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DOI：
10.1186/s40364-023-00477-6
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发表时间：
2023-04-13
影响因子：
11.1
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中科院分区：
文献类型：
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骨关节炎（OA）是世界上最常见的年龄相关性疾病。软骨细胞的增殖和合成能力随年龄增长而下降，这是OA发生的主要原因。然而，软骨细胞衰老的内在机制仍不清楚。本研究旨在探讨一种新的长链非编码RNA（lncRNA）AC006064.4-201在软骨细胞衰老和OA进展中的作用，并阐明其潜在的分子机制。使用蛋白质印迹、定量实时聚合酶链反应（qRT-PCR）、免疫荧光（IF）和β-半乳糖苷酶染色评估AC006064.4-201在软骨细胞中的功能。采用RPD-MS、荧光原位杂交（FISH）、RNA免疫沉淀（RIP）和RNA下拉试验评价了AC 006064.4 -201与多聚嘧啶片段结合蛋白1（PTBP 1）以及细胞周期蛋白依赖性激酶抑制剂1B（CDKN 1B）之间的相互作用。使用小鼠模型研究AC006064.4-201在体内创伤后和年龄相关OA中的作用。我们的研究表明，AC006064.4-201在衰老和退行性变的人软骨中表达下调，可以缓解软骨细胞的衰老和调节软骨细胞的代谢。在机械上，AC 006064.4 -201直接与PTBP 1相互作用并阻断PTBP 1与CDKN 1B mRNA之间的结合，从而使CDKN 1B mRNA不稳定并降低CDKN 1B的翻译。体内实验与体外实验结果一致。AC006064.4-201/PTBP 1/CDKN 1B轴在OA的发生发展中起重要作用，为今后OA的早期诊断和治疗提供了新的分子标志物。AC006064.4-201机构示意图。AC006064.4-201作用机制示意图在线版本包含补充材料，可通过10.1186/s40364-023-00477-6获得。
Osteoarthritis (OA) is the most prevalent age-related disease in the world. Chondrocytes undergo an age-dependent decline in their proliferation and synthetic capacity, which is the main cause of OA development. However, the intrinsic mechanism of chondrocyte senescence is still unclear. This study aimed to investigate the role of a novel long non-coding RNA (lncRNA), AC006064.4–201 in the regulation of chondrocyte senescence and OA progression and to elucidate the underlying molecular mechanisms. The function of AC006064.4–201 in chondrocytes was assessed using western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence (IF) and β-galactosidase staining. The interaction between AC006064.4–201 and polypyrimidine tract-binding protein 1 (PTBP1), as well as cyclin-dependent kinase inhibitor 1B (CDKN1B), was evaluated using RPD-MS, fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP) and RNA pull-down assays. Mice models were used to investigate the role of AC006064.4–201 in post-traumatic and age-related OA in vivo. Our research revealed that AC006064.4–201 was downregulated in senescent and degenerated human cartilage, which could alleviate senescence and regulate metabolism in chondrocytes. Mechanically, AC006064.4–201 directly interacts with PTBP1 and blocks the binding between PTBP1 and CDKN1B mRNA, thereby destabilizing CDKN1B mRNA and decreasing the translation of CDKN1B. The in vivo experiments were consistent with the results of the in vitro experiments. The AC006064.4–201/PTBP1/CDKN1B axis plays an important role in OA development and provides new molecular markers for the early diagnosis and treatment of OA in the future. Schematic diagram of AC006064.4–201 mechanism. A schematic diagram of the mechanism underlying the effect of AC006064.4–201 The online version contains supplementary material available at 10.1186/s40364-023-00477-6.
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影响因子：
12.7
作者：
Li X;Tian BM;Deng DK;Liu F;Zhou H;Kong DQ;Qu HL;Sun LJ;He XT;Chen FM
通讯作者：
Chen FM
影响因子：
--
作者：
Hootman, JM;Helmick, CG
通讯作者：
Helmick, CG
影响因子：
7.8
作者：
Ogrodnik M
通讯作者：
Ogrodnik M
影响因子：
37.3
作者：
Li, Mengwei;Liu, Guangxiang;Jin, Xinrong;Guo, Hongqian;Setrerrahmane, Sarra;Xu, Xindi;Li, Tiantian;Lin, Yunfei;Xu, Hanmei
通讯作者：
Xu, Hanmei
影响因子：
4.5
作者：
Amir-Ahmady, B;Boutz, PL;Black, DL
通讯作者：
Black, DL