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

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...

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Bibliographic Details
Published in:Scientific reports 2016-01, Vol.6 (1), p.18743-18743, Article 18743
Main Authors: Aini, Hailati, Itaka, Keiji, Fujisawa, Ayano, Uchida, Hirokuni, Uchida, Satoshi, Fukushima, Shigeto, Kataoka, Kazunori, Saito, Taku, Chung, Ung-il, Ohba, Shinsuke
Format: Article
Language:English
Subjects:
Animals
Arthritis
Cartilage diseases
Cartilage, Articular - metabolism
Cartilage, Articular - pathology
Chondrocytes
Disease
Disease Models, Animal
Gene Expression
Gene Transfer Techniques
Genes, Reporter
Geriatrics
Injections, Intra-Articular
Knee
Mice
Micelles
Nanocomposites - administration & dosage
Nanocomposites - chemistry
Older people
Osteoarthritis
Osteoarthritis - genetics
Osteoarthritis - metabolism
Osteoarthritis - pathology
Osteoarthritis - therapy
Osteoarthritis, Knee - genetics
Osteoarthritis, Knee - metabolism
Osteoarthritis, Knee - pathology
Osteoarthritis, Knee - therapy
Polyethylene glycol
RNA, Messenger - administration & dosage
RNA, Messenger - chemistry
RNA, Messenger - genetics
Runx1 protein
Transcription factors
Transcription Factors - genetics
Transcription Factors - metabolism
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep18743