载有circ_0003251的聚乳酸-羟基乙酸共聚物微球通过miR-637/AKT1轴减轻椎间盘退变。

PLGA-microspheres carried circ_0003251 alleviate intervertebral disc degeneration via the miR-637/AKT1 axis.

作者信息

Xiong Shouliang, Zhao Quanlai, Zhang Yu, Li Yifeng, Yang Xiaoming, Xiao Liang

机构信息

Department of Orthopedics, Yijishan Hospital of Wannan Medical College, No. 2 Zheshan West Road, Wuhu, 241001, Anhui, China.

Department of Spine Surgery, Yijishan Hospital of Wannan Medical College, No. 2 Zheshan West Road, Wuhu, 241001, Anhui, China.

出版信息

J Transl Med. 2025 Jul 25;23(1):840. doi: 10.1186/s12967-025-06800-z.

DOI:10.1186/s12967-025-06800-z

PMID:40713764

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12297672/

Abstract

BACKGROUND

Circular RNA (circRNA) plays a pivotal role in regulating nucleus pulposus cells (NPCs) function, making it a promising therapeutic target for intervertebral disc degeneration (IDD). This study aimed to identify circRNA closely associated with IDD and assess their potential as therapeutic target.

METHODS

Circ_0003251 was identified via circRNA sequencing and validated in degenerated human nucleus pulposus (NP) tissues. Its properties were characterized using Sanger sequencing, oligo(dT) primers, RNase R treatment, and fluorescence in situ hybridization. Functional experiments assessed its role in vitro, while molecular mechanisms were explored through luciferase reporter assays, RNA-binding protein immunoprecipitation, and immunofluorescence. To assess therapeutic potential, circ_0003251 was encapsulated in PLGA (poly(lactic-co-glycolic acid)) microspheres (MS) and evaluated in vitro and in vivo.

RESULTS

Circ_0003251 expression was significantly downregulated in degenerated NPCs and NP tissues. Its upregulation enhanced NPCs proliferation, extracellular matrix synthesis, and reduced apoptosis. Mechanistically, circ_0003251 acted as a miR-637 sponge, inhibiting AKT1 suppression and alleviating NPCs degeneration. PLGA MS successfully delivered circ_0003251, enhancing its therapeutic effect and delaying IDD in vivo.

CONCLUSION

Circ_0003251 was a promising biomarker and therapeutic target for IDD. PLGA MS delivery ensured effective application, offering a novel strategy for IDD treatment.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1186/s12967-025-06800-z.

摘要

背景

环状RNA（circRNA）在调节髓核细胞（NPCs）功能中起关键作用，使其成为椎间盘退变（IDD）的一个有前景的治疗靶点。本研究旨在鉴定与IDD密切相关的circRNA并评估其作为治疗靶点的潜力。

方法

通过circRNA测序鉴定出Circ_0003251，并在退变的人髓核（NP）组织中进行验证。使用桑格测序、寡聚（dT）引物、RNase R处理和荧光原位杂交对其特性进行表征。功能实验评估其在体外的作用，同时通过荧光素酶报告基因测定、RNA结合蛋白免疫沉淀和免疫荧光探索分子机制。为评估治疗潜力，将circ_0003251封装在聚乳酸-乙醇酸共聚物（PLGA）微球（MS）中并在体外和体内进行评估。

结果

Circ_0003251在退变的NPCs和NP组织中的表达显著下调。其上调增强了NPCs的增殖、细胞外基质合成并减少了细胞凋亡。机制上，circ_0003251作为miR-637的海绵，抑制AKT1的抑制并减轻NPCs退变。PLGA MS成功递送circ_0003251，增强了其治疗效果并在体内延缓了IDD。