一种可诱导的长非编码RNA,LncZFHX2,促进DNA修复以调解骨关节炎病理
Weiyu Ni1, Haitao Zhang1, Zixuan Mei1
1Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, Zhejiang Province, China; Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, China.
Redox biology
|August 26, 2023
概括
这项研究确定LncZFHX2,一个长非编码RNA,对于在缺氧下维持软骨平衡至关重要. 它的缺失加速了细胞衰老和软骨退化,突出了一个新的缺氧激活的DNA修复途径.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 软骨的平衡依赖于细胞维持适当的表型和新陈代谢.
- 成年人关节软骨中非血管性软骨中的软骨细胞在低氧条件下存活,在这种条件下,氧张力会影响新陈代谢和蛋白质甘氨酸的合成.
研究的目的:
- 为了研究长非编码RNAs (lncRNAs) 在低氧条件下的软骨平衡中的作用.
- 为了确定特定的lncRNAs参与状细胞对低氧条件的反应.
主要方法:
- 鉴定LncZFHX2是软骨中低氧上调的lncRNA,由HIF-1α调节.
- 在体外和体内实验涉及LncZFHX2淘汰和冠状细胞条件淘汰的实验.
- 对细胞衰老,细胞外基质代谢,DNA损伤和RIF1表达的分析.
主要成果:
- LncZFHX2倒置加速了状细胞衰老,破坏了细胞外基质代谢,并增加了DNA损伤.
- LncZFHX2通过与KLF4的转录复合体调节RIF1的表达,促进冠状细胞DNA修复.
- LncZFHX2的冠状细胞特异性淘汰加剧了受伤引起的软骨退化.
结论:
- LncZFHX2是一种新型缺氧激活的lncRNA,对于维持胆细胞功能和软骨平衡至关重要.
- 确定了涉及LncZFHX2和RIF1的缺氧激活的DNA修复途径,这对于骨关节炎的矩阵稳定性至关重要.
- LncZFHX2对软骨退化起着保护作用,特别是在低氧压力下.
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