由于机械过载而降低RPL35的调节,通过Hedgehog-Gli1信号传递促进了软骨细胞衰老和骨关节炎的发展
Jinjian Zhu1,2,3, Liangliang Liu1,2,3, Rengui Lin1,2,3
1Department of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics·Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degenerative Disease, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510280, China.
Journal of orthopaedic translation
|April 10, 2024
概括
过度表达Ribosomal蛋白L35 (RPL35) 保护胆红细胞免受退化,并可能通过调节代谢代谢和细胞衰老来提供骨关节炎 (OA) 的新疗法.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 整形外科 整形外科 整形外科
背景情况:
- 骨关节炎 (OA) 的发病包括状细胞的代谢和细胞衰老.
- 目前对OA的药物治疗有局限性,需要新的治疗点.
- 在OA中,核糖体蛋白L35 (RPL35) 的作用尚未完全理解.
研究的目的:
- 研究RPL35在状细胞代谢中的作用.
- 确定RPL35过度表达是否可以在小鼠模型中延迟OA的进展.
- 探索RPL35作为OA治疗点的潜力.
主要方法:
- 在机械负荷下对红细胞的RNA测序.
- 通过手术破坏稳定和压缩负载在小鼠中诱导实验性OA.
- 在小鼠OA模型中,腺病毒介导的RPL35过度表达.
- 使用骨关节炎研究学会国际分数对软骨退化的评估.
- 通过免疫染色和西方布洛特分析蛋白质水平.
主要成果:
- 红细胞中过度机械负荷时,RPL35蛋白表达减少.
- 较高的RPL35水平保护了关节性肌肉细胞免受退化.
- 通过刺路径,RPL35敲击诱导了状细胞衰老和调节的合成/代谢标记物.
- 在小鼠模型中,RPL35的过度表达延迟了OA的进展.
结论:
- RPL35在软骨细胞功能和OA病变发生过程中发挥着关键作用.
- 关节内RPL35注射显示了OA预防和治疗的潜力.
- 准RPL35为骨关节炎提供了一个新的治疗策略.
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