长非编码RNAAPDC在骨和脂肪组织的新陈代谢中起着重要的调节作用
Yao Liu1,2, Zoe Xiaofang Zhu2, Elissa K Zboinski2
1State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
RNA biology
|November 13, 2023
概括
长非编码RNA lncR-APDC调节骨和脂肪的新陈代谢. 它的缺乏会损害骨形成,但会促进脂肪和骨质细胞的发育,这表明对代谢失衡的治疗潜力.
科学领域:
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
- 代谢研究研究 代谢研究
背景情况:
- 长非编码RNA (lncR) ANRIL与各种疾病有关.
- 在骨和脂肪组织代谢中IncR-ANRIL的作用尚不清楚.
- 这项研究研究了老鼠的ortolog,IncR-APDC,其在骨和脂肪代谢中的功能.
研究的目的:
- 阐明lncR-APDC在骨和脂肪组织代谢中的功能.
- 研究IncR-APDC在骨质生成,脂肪生成和骨质细胞生成中的调节机制.
- 探索 lncR-APDC 在代谢障碍中的潜在治疗应用.
主要方法:
- 使用了小鼠骨髓干细胞 (BMSC) 和人类骨质母细胞 (hFOB).
- 创建了 lncR-APDC 删除和过度表达细胞模型.
- 进行了体内研究,比较APDC-Knockout (KO) 和野生型小鼠.
- 分析了基因表达,蛋白质水平和信号通路 (miR-99a,KDM6B,Hox,MAPK/p38,TLR4/MyD88) 的情况.
主要成果:
- 在小鼠和人类细胞的早期骨质生成过程中,lncR-APDC的表达增加.
- lncR-APDC缺乏促进了脂肪生成和骨质细胞生成,同时损害了骨质生成.
- 过度表达lncR-APDC具有相反的效果,刺激骨质生成并抑制脂肪生成/骨质细胞生成.
- lncR-APDC调节KDM6B的表达,并与miR-99a相互作用,影响miR-99a/KDM6B/Hox通路.
- lncR-APDC通过MAPK/p38和TLR4/MyD88信号传递来调节骨质组-骨质生成平衡.
结论:
- lncR-APDC是骨和脂肪组织代谢的关键调节者.
- 在lncR-APDC/miR-99a/KDM6B/Hox路径是其骨质生成功能的关键.
- lncR-APDC通过MAPK/p38和TLR4/MyD88.88,影响骨质结晶-骨质生成平衡.
- lncR-APDC对影响骨和脂肪组织的代谢失衡具有潜在的治疗标.
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