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) |