介质细胞钟调节TMJ恒温和脂质代谢节奏随着年龄的增长
1State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Orthodontics, West China School of Stomatology, Sichuan University, Chengdu, China.
Journal of dental research
|December 18, 2025
概括
衰老会破坏关节 (TMJ) 的软骨. 一项研究发现,介质细胞的昼夜时钟,特别是BMAL1,对关节健康至关重要,PRG4补充剂可以对抗与年龄相关的关节退化.
科学领域:
- 生物遗传学 生物遗传学
- 时间生物学 时间生物学
- 整形外科 整形外科 整形外科
背景情况:
- 骨关节炎 (OA) 是一种常见的关节疾病,衰老是主要的危险因素.
- 循环时钟调节组织平衡,但它们在肌关节衰老中的作用尚不清楚.
- 了解TMJ昼夜调节对于解决与年龄相关的退化至关重要.
研究的目的:
- 研究介质细胞昼夜时钟在老化过程中维护肌关节骨髓完整性的作用.
- 阐明昼夜调节器影响TMJ恒温的分子机制.
- 探索与年龄相关的关节退行症的潜在慢性治疗策略.
主要方法:
- 利用了老化和转基因小鼠模型,这些小鼠模型缺乏中细胞中核心昼夜调节器Bmal1.
- 分析了TMJ状骨的骨髓完整性,软骨分层和骨下骨架构.
- 研究了BMAL1对Prg4转录,TGF-β信号传递和脂质代谢的调节.
- 在关节内给定昼夜计时的重组PRG4,以评估治疗效果.
主要成果:
- 介质细胞Bmal1的损失诱导了渐进的TMJ骨质突变,类似于与年龄相关的退化.
- 发现BMAL1直接调节PRG4,抑制TGF-β信号,并维持脂质代谢节奏.
- 循环定时的PRG4给药在Bmal1突变和老年小鼠中部分恢复了软骨完整性.
结论:
- 介质细胞的昼夜时钟对于在衰老过程中保持TMJ骨髓完整性至关重要.
- 由介质细胞钟驱动的PRG4-TGF-β信号轴,将昼夜调节与关节平衡和脂质代谢相结合.
- 慢性治疗PRG4补充剂是一个有希望的策略,以减轻与年龄相关的关节退化.
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