抑制lysyl氧化酶可以防止病理性软骨化
Ilaria Bernabei1, Elodie Faure1, Mario Romani2
1Service of Rheumatology, Department of Musculoskeletal Medicine, Lausanne University Hospital and University of Lausanne; Lausanne, Switzerland.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
|January 6, 2024
概括
酸氧化酶 (LOXL) 酶在软骨化和相关关节病中至关重要. 抑制LOXL通过影响矩阵交叉连接,纤维化标记物和软骨细胞分化来减少化,提供潜在的治疗点.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 病理学 病理学 病理学
背景情况:
- 溶氧化酶 (LOXL) 是关键的酶,在骨化过程中对原蛋白和弹性质进行交叉链接.
- 对于LOXL在病理性关节软骨化中的作用,这是关节病的标志性特征,尚不清楚.
研究的目的:
- 调查LOXL在软骨化中的作用,独立于它们的交联活性.
- 探索LOXL作为治疗关节病的软骨化治疗的潜在治疗标.
主要方法:
- 使用β-aminoproprionitrile (BAPN) 抑制LOXL在小鼠和人类冠状细胞中,以及在经过月经切除的小鼠中.
- 对化基因 (Anx5,Pit1,Pit2),原纤维化标记物 (Col1,Col3),状细胞分化标记物 (Runx2,COL10),IL-6和活性氧物种 (ROS) 的分析.
- 无偏见的转录组分析,以确定LOXL基因与化/增高通路之间的相关性.
主要成果:
- BAPN治疗显著降低了软质细胞和小鼠关节的化.
- LOXL抑制降低了细胞外矩阵交叉链接,纤维化标记物,冠状细胞缩,IL-6释放和ROS生产.
- 转录组分析显示,LOXL基因与涉及化,高化和细胞外矩阵催化作用的途径之间存在着保存的正相关性,跨物种和组织.
结论:
- 通过多种机制,LOXL酶在状细胞化中发挥着重要作用.
- 抑制LOXL有效地减少了软骨化,这表明LOXL是关节病的有希望的治疗点.
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