Messenger RNA delivery of a cartilage-anabolic transcription factor as a disease-modifying strategy for osteoarthritis treatment

被引：103

作者：

Aini, Hailati ^{[1
]}

Itaka, Keiji ^{[2
]}

Fujisawa, Ayano ^{[1
]}

Uchida, Hirokuni ^{[2
]}

Uchida, Satoshi ^{[2
]}

Fukushima, Shigeto ^{[5
]}

Kataoka, Kazunori ^{[2
,5
]}

Saito, Taku ^{[3
,4
]}

Chung, Ung-il ^{[1
,2
]}

Ohba, Shinsuke ^{[1
]}

机构：

[1] Univ Tokyo, Dept Bioengn, Grad Sch Engn, Bunkyo Ku, Tokyo 1138656, Japan

[2] Univ Tokyo, Ctr Dis Biol & Integrat Med, Lab Clin Biotechnol, Grad Sch Med,Bunkyo Ku, Tokyo 1130033, Japan

[3] Univ Tokyo, Dept Bone & Cartilage Regenerat Med, Grad Sch Med, Bunkyo Ku, Tokyo 1130033, Japan

[4] Univ Tokyo, Dept Sensory & Motor Syst Med, Grad Sch Med, Bunkyo Ku, Tokyo 1130033, Japan

[5] Univ Tokyo, Grad Sch Engn, Dept Mat Engn, Bunkyo Ku, Tokyo 1138656, Japan

来源：

SCIENTIFIC REPORTS | 2016年 / 6卷

基金：

日本科学技术振兴机构; 日本学术振兴会;

关键词：

N-SUBSTITUTED POLYASPARTAMIDES; ARTICULAR-CARTILAGE; GLOBAL BURDEN; SIDE-CHAIN; EXPRESSION; SOX9; DIFFERENTIATION; RUNX1; IDENTIFICATION; PLURIPOTENCY;

D O I：

10.1038/srep18743

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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 copolymerbased 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.

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