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Stress-activated miR-204 governs senescent phenotypes of chondrocytes to promote osteoarthritis development

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Title
Stress-activated miR-204 governs senescent phenotypes of chondrocytes to promote osteoarthritis development
Author(s)
Donghyun Kang; Jungkwon Shin; Yongsik Cho; Hyeon-Seop Kim; Young-Ran Gu; Haedong Kim; Kwon Tae You; Chang, MJ; Chang, CB; Kang, SB; Jong-Seo Kim; V. Narry Kim; Jin-Hong Kim
Publication Date
2019-04
Journal
SCIENCE TRANSLATIONAL MEDICINE, v.11, no.486, pp.eaar6659 -
Publisher
AMER ASSOC ADVANCEMENT SCIENCE
Abstract
Copyright © 2019 The Authors, A progressive loss of cartilage matrix leads to the development of osteoarthritis (OA). Matrix homeostasis is disturbed in OA cartilage as the result of reduced production of cartilage-specific matrix and increased secretion of catabolic mediators by chondrocytes. Chondrocyte senescence is a crucial cellular event contributing to such imbalance in matrix metabolism during OA development. Here, we identify miR-204 as a markedly up-regulated microRNA in OA cartilage. miR-204 is induced by transcription factors GATA4 and NF-B in response to senescence signals. Up-regulated miR-204 simultaneously targets multiple components of the sulfated proteoglycan (PG) biosynthesis pathway, effectively shutting down PG anabolism. Ectopic expression of miR-204 in joints triggers spontaneous cartilage loss and OA development, whereas miR-204 inhibition ameliorates experimental OA, with concomitant recovery of PG synthesis and suppression of inflammatory senescence-associated secretory phenotype (SASP) factors in cartilage. Collectively, we unravel a stress-activated senescence pathway that underlies disrupted matrix homeostasis in OA cartilage
URI
https://pr.ibs.re.kr/handle/8788114/6471
ISSN
1946-6234
Appears in Collections:
Center for RNA Research(RNA 연구단) > Journal Papers (저널논문)
Files in This Item:
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