RRC ID 37885
著者 Aini H, Itaka K, Fujisawa A, Uchida H, Uchida S, Fukushima S, Kataoka K, Saito T, Chung UI, Ohba S.
タイトル Messenger RNA delivery of a cartilage-anabolic transcription factor as a disease-modifying strategy for osteoarthritis treatment.
ジャーナル Sci Rep
Abstract 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.
巻・号 6
ページ 18743
公開日 2016-1-5
DOI 10.1038/srep18743
PII srep18743
PMID 26728350
PMC PMC4700530
MeSH Animals Cartilage, Articular / metabolism* Cartilage, Articular / pathology Disease Models, Animal Gene Expression Gene Transfer Techniques Genes, Reporter Injections, Intra-Articular Mice Micelles Nanocomposites / administration & dosage Nanocomposites / chemistry Osteoarthritis / genetics* Osteoarthritis / metabolism* Osteoarthritis / pathology Osteoarthritis / therapy Osteoarthritis, Knee / genetics Osteoarthritis, Knee / metabolism Osteoarthritis, Knee / pathology Osteoarthritis, Knee / therapy RNA, Messenger / administration & dosage* RNA, Messenger / chemistry RNA, Messenger / genetics* Transcription Factors / genetics* Transcription Factors / metabolism
IF 3.998
引用数 38
WOS 分野 RHEUMATOLOGY
リソース情報
ヒト・動物細胞 HeLa(RCB0007) 293(RCB1637)