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

Cited 26 time in Web of Science Cited 27 time in Scopus
Authors
Kang, Donghyun; Shin, Jungkwon; Cho, Yongsik; Kim, Hyeon-Seop; Gu, Young-Ran; Kim, Haedong; You, Kwon Tae; Chang, Moon Jong; Chang, Chong Bum; Kang, Seung-Baik; Kim, Jong-Seo; Kim, V. Narry; Kim, Jin-Hong
Issue Date
2019-04
Citation
Science Translational Medicine, Vol.11 No.486, p. eaar6659
Abstract
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-kappa 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.
ISSN
1946-6234
URI
https://hdl.handle.net/10371/171955
DOI
https://doi.org/10.1126/scitranslmed.aar6659
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College of Natural Sciences (자연과학대학)Dept. of Biological Sciences (생명과학부)Journal Papers (저널논문_생명과학부)
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