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IL16 作为新型 miR-81 的靶基因调节骨关节炎进展。

IL16 Regulates Osteoarthritis Progression as a Target Gene of Novel-miR-81.

机构信息

Research Centre of Basic Intergrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, P.R. China.

Traditional Chinese Medicine Innovation Research Center, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Guangzhou University of Chinese Medicine, Shenzhen, P.R. China.

出版信息

Cartilage. 2024 Jun;15(2):175-183. doi: 10.1177/19476035231168387. Epub 2023 Apr 21.

DOI:10.1177/19476035231168387
PMID:37086007
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11368893/
Abstract

OBJECTIVE

Functional polymorphisms of interleukin 16 (IL16) have been reported to be closely related to the risk of osteoarthritis (OA). However, how IL16 affects OA remains unclear. In this study, the role of IL16 in OA and the possible mechanisms were examined.

METHODS

We established a meniscal/ligament injury (MLI) post-traumatic OA model in Sprague Dawley rats and an IL1β-induced ADTC5 cells OA model. We detected the expression of IL16, novel-miR-81, MMP3, and MMP13 by quantitative real-time polymerase chain reaction. Western blot was performed to detect the expression of IL16, MMP3, and MMP13. The association between IL16 and novel-miR-81 was confirmed by luciferase reporter assay. Hematoxylin and eosin staining, Safranin O and Fast Green staining, and immunohistochemical staining were performed to clarify the effect of intra-articular injection of novel-miR-81 agomir in rats OA model.

RESULTS

IL16 was upregulated in OA model. Knockdown of IL16 and overexpression of novel-miR-81 downregulated the expression of MMP3 and MMP13. Importantly, IL16 was a key target of novel-miR-81. Intra-articular injection of novel-miR-81 agomir could attenuate OA progression in rats OA model.

CONCLUSION

Novel-miR-81 targeted IL16 to relieve OA, suggesting that novel-miR-81and IL16 may be new therapeutic targets for OA.

摘要

目的

白细胞介素 16（IL16）的功能多态性与骨关节炎（OA）的风险密切相关。然而，IL16 如何影响 OA 尚不清楚。在这项研究中，研究了 IL16 在 OA 中的作用及其可能的机制。

方法

我们建立了半月板/韧带损伤（MLI）创伤后 OA 模型和 IL1β诱导的 ADTC5 细胞 OA 模型。通过定量实时聚合酶链反应检测 IL16、新型-miR-81、MMP3 和 MMP13 的表达。通过 Western blot 检测 IL16、MMP3 和 MMP13 的表达。通过荧光素酶报告试验证实了 IL16 与新型-miR-81 的关联。通过苏木精和伊红染色、番红 O 和 Fast Green 染色以及免疫组织化学染色，阐明了新型-miR-81 激动剂在大鼠 OA 模型中的关节内注射对 OA 的影响。

结果

OA 模型中 IL16 上调。IL16 敲低和新型-miR-81 过表达下调 MMP3 和 MMP13 的表达。重要的是，IL16 是新型-miR-81 的关键靶点。新型-miR-81 激动剂的关节内注射可减轻大鼠 OA 模型中的 OA 进展。

结论

新型-miR-81 靶向 IL16 以缓解 OA，提示新型-miR-81 和 IL16 可能是 OA 的新治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd0a/11368893/678fd6c2fdc2/10.1177_19476035231168387-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd0a/11368893/c52ac90ec4f6/10.1177_19476035231168387-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd0a/11368893/c39d749e5e31/10.1177_19476035231168387-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd0a/11368893/5bbe923f05a0/10.1177_19476035231168387-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd0a/11368893/842590eabc24/10.1177_19476035231168387-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd0a/11368893/04e53f529e4d/10.1177_19476035231168387-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd0a/11368893/678fd6c2fdc2/10.1177_19476035231168387-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd0a/11368893/c52ac90ec4f6/10.1177_19476035231168387-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd0a/11368893/c39d749e5e31/10.1177_19476035231168387-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd0a/11368893/5bbe923f05a0/10.1177_19476035231168387-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd0a/11368893/842590eabc24/10.1177_19476035231168387-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd0a/11368893/04e53f529e4d/10.1177_19476035231168387-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd0a/11368893/678fd6c2fdc2/10.1177_19476035231168387-fig6.jpg

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