PLGA-microspheres carried circ_0003251 alleviate intervertebral disc degeneration via the miR-637/AKT1 axis
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 th...
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| Format: | Article |
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BMC
2025-07-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-025-06800-z |
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| author | Shouliang Xiong Quanlai Zhao Yu Zhang Yifeng Li Xiaoming Yang Liang Xiao |
| author_facet | Shouliang Xiong Quanlai Zhao Yu Zhang Yifeng Li Xiaoming Yang Liang Xiao |
| author_sort | Shouliang Xiong |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-0215570427de4595a9880720aecc28cf |
| institution | Kabale University |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-0215570427de4595a9880720aecc28cf2025-08-20T03:42:56ZengBMCJournal of Translational Medicine1479-58762025-07-0123111910.1186/s12967-025-06800-zPLGA-microspheres carried circ_0003251 alleviate intervertebral disc degeneration via the miR-637/AKT1 axisShouliang Xiong0Quanlai Zhao1Yu Zhang2Yifeng Li3Xiaoming Yang4Liang Xiao5Department of Orthopedics, Yijishan Hospital of Wannan Medical CollegeDepartment of Spine Surgery, Yijishan Hospital of Wannan Medical CollegeKey Laboratory of Non-Coding RNA Transformation Research of Anhui Higher Education InstitutionDepartment of Spine Surgery, Yijishan Hospital of Wannan Medical CollegeDepartment of Spine Surgery, Yijishan Hospital of Wannan Medical CollegeDepartment of Spine Surgery, Yijishan Hospital of Wannan Medical CollegeAbstract 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.https://doi.org/10.1186/s12967-025-06800-zIntervertebral disc degenerationNucleus pulposus cellsCirc_0003251Microspheres |
| spellingShingle | Shouliang Xiong Quanlai Zhao Yu Zhang Yifeng Li Xiaoming Yang Liang Xiao PLGA-microspheres carried circ_0003251 alleviate intervertebral disc degeneration via the miR-637/AKT1 axis Journal of Translational Medicine Intervertebral disc degeneration Nucleus pulposus cells Circ_0003251 Microspheres |
| title | PLGA-microspheres carried circ_0003251 alleviate intervertebral disc degeneration via the miR-637/AKT1 axis |
| title_full | PLGA-microspheres carried circ_0003251 alleviate intervertebral disc degeneration via the miR-637/AKT1 axis |
| title_fullStr | PLGA-microspheres carried circ_0003251 alleviate intervertebral disc degeneration via the miR-637/AKT1 axis |
| title_full_unstemmed | PLGA-microspheres carried circ_0003251 alleviate intervertebral disc degeneration via the miR-637/AKT1 axis |
| title_short | PLGA-microspheres carried circ_0003251 alleviate intervertebral disc degeneration via the miR-637/AKT1 axis |
| title_sort | plga microspheres carried circ 0003251 alleviate intervertebral disc degeneration via the mir 637 akt1 axis |
| topic | Intervertebral disc degeneration Nucleus pulposus cells Circ_0003251 Microspheres |
| url | https://doi.org/10.1186/s12967-025-06800-z |
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