Messenger RNA delivery of a cartilage-anabolic transcription factor as a disease-modifying strategy for osteoarthritis treatment.
Messenger RNA delivery of a cartilage-anabolic transcription factor as a disease-modifying strategy for osteoarthritis treatment.
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DOI：
10.1038/srep18743
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发表时间：
2016-01-05
影响因子：
4.6
通讯作者：
Ohba S
中科院分区：
文献类型：
--
作者：
Aini H;Itaka K;Fujisawa A;Uchida H;Uchida S;Fukushima S;Kataoka K;Saito T;Chung UI;Ohba S
骨关节炎（OA）是一种慢性退行性关节疾病，也是老年人口的主要健康问题。目前还没有缓解疾病的骨关节炎药物（DMOAD）可供临床使用。在这里，我们提出了一种针对 OA 的疾病缓解策略，重点是使用基于聚乙二醇 (PEG)-聚氨基酸嵌段共聚物的聚合纳米胶束传递治疗性转录因子的信使 RNA (mRNA)。当携带软骨合成代谢、runt 相关转录因子 (RUNX) 1 mRNA 的复合纳米胶束注射到小鼠 OA 膝关节时，与未治疗对照相比，OA 进展得到显着抑制。注射 RUNX1 的膝关节软骨细胞中软骨合成代谢标志物的表达和增殖均增强。因此，这项研究为通过原位 mRNA 递送治疗性转录因子来治疗 OA 等退行性疾病提供了概念证明；所提出的方法将直接将疾病保护或组织再生因素的基本发现与疾病治疗联系起来。
Osteoarthritis (OA) is a chronic degenerative joint disease and a major health problem in the elderly population. No disease-modifying osteoarthritis drug (DMOAD) has been made available for clinical use. Here we present a disease-modifying strategy for OA, focusing on messenger RNA (mRNA) delivery of a therapeutic transcription factor using polyethylene glycol (PEG)-polyamino acid block copolymer-based polyplex nanomicelles. When polyplex nanomicelles carrying the cartilage-anabolic, runt-related transcription factor (RUNX) 1 mRNA were injected into mouse OA knee joints, OA progression was significantly suppressed compared with the non-treatment control. Expressions of cartilage-anabolic markers and proliferation were augmented in articular chondrocytes of the RUNX1-injected knees. Thus, this study provides a proof of concept of the treatment of degenerative diseases such as OA by the in situ mRNA delivery of therapeutic transcription factors; the presented approach will directly connect basic findings on disease-protective or tissue-regenerating factors to disease treatment.