模块化外泌体运载LINC01001调控IGF2BP2的m6A选择性识别功能防治骨关节炎的机制研究

骨关节炎（OA）是一种常见的发病机理不明的致残疾病，临床尚无有效干预OA进展的方法。我们前期建立模块化外泌体技术，实现核酸类药物的高效递送，并探索了其在组织再生方面的应用。经生物信息学分析和预实验发现LINC01001可以通过调控IGF2BP2的m6A选择性识别功能影响软骨表型相关基因，维持软骨稳态。经模块化外泌体技术构建高表达LINC01001的外泌体（L1001-Exos）并进行鉴定和表征；体外实验验证L1001-Exos维持软骨稳态的作用；体内实验进一步验证L1001-Exos延缓或逆转OA进展的潜能。研究递送核酸类药物的模块化外泌体L1001-Exos，可深入探索其针对病因精准治疗OA的潜力。本项目的顺利实施，不仅可以明确LINC01001对于m6A选择性识别功能和表观遗传的调控，及其对软骨表型相关基因和软骨稳态的影响，为针对OA发病机理制定精准治疗策略提供理论基础和新思路。

Osteoarthritis (OA) is a common debilitating disease with unknown pathogenesis, and hence, there is no effective clinical treatment for preventing the progression of OA. We established a ‘modularized exosome’ technology to achieve efficient delivery of nucleic acid-based drugs, and explored its application in tissue regeneration. By performing bioinformatics analysis and preliminary experiments, we found that LINC01001 influenced the genes related to cartilage phenotype and maintained cartilage homeostasis by regulating the m6A-selective recognition function of IGF2BP2. The ‘modularized exosome’ L1001-Exos with high LINC01001 expression level was produced by modularized exosome technology and identified. An in vitro study was performed to demonstrate the role of L1001-Exos in maintaining cartilage homeostasis. In vivo experiments further demonstrated the potential of L1001-Exos to delay or reverse the progression of OA. The study of the ‘modularized exosome’ L1001-Exos, which delivers nucleic acid-based drugs, can further explore its potential for the precise and specific treatment of OA on the basis of its aetiology. The results of such a study can not only clarify the regulatory effect of LINC01001 on the m6A-selective recognition function and epigenetic inheritance but also its effect on the genes related to cartilage phenotype and homeostasis, thereby providing a theoretical basis and a new perspective on the formulation of precise treatment strategies targeting the pathogenesis of OA.