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Tankyrase inhibition preserves osteoarthritic cartilage by coordinating cartilage matrix anabolism via effects on SOX9 PARylation

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Title
Tankyrase inhibition preserves osteoarthritic cartilage by coordinating cartilage matrix anabolism via effects on SOX9 PARylation
Author(s)
Sukyeong Kim; Sangbin Han; Yeongjae Kim; Hyeon-Seop Kim; Young-Ran Gu; Donghyun Kang; Yongsik Cho; Hyeonkyeong Kim; Jeeyeon Lee; Yeyoung Seo; Chang, MJ; Chang, CB; Kang, S-B
Publication Date
2019-10
Journal
NATURE COMMUNICATIONS, v.10, no., pp.4898 -
Publisher
NATURE PUBLISHING GROUP
Abstract
Osteoarthritis (OA) is a prevalent degenerative disease, which involves progressive and irreversible destruction of cartilage matrix. Despite efforts to reconstruct cartilage matrix in osteoarthritic joints, it has been a difficult task as adult cartilage exhibits marginal repair capacity. Here we report the identification of tankyrase as a regulator of the cartilage anabolism axis based on systems-level factor analysis of mouse reference populations. Tankyrase inhibition drives the expression of a cartilage-signature matrisome and elicits a transcriptomic pattern that is inversely correlated with OA progression. Furthermore, tankyrase inhibitors ameliorate surgically induced OA in mice, and stem cell transplantation coupled with tankyrase knockdown results in superior regeneration of cartilage lesions. Mechanistically, the pro-regenerative features of tankyrase inhibition are mainly triggered by uncoupling SOX9 from a poly(ADP-ribosyl)ation (PARylation)-dependent protein degradation pathway. Our findings provide insights into the development of future OA therapies aimed at reconstruction of articular cartilage. © The Author(s) 2019
URI
https://pr.ibs.re.kr/handle/8788114/6562
ISSN
2041-1723
Appears in Collections:
Center for RNA Research(RNA 연구단) > Journal Papers (저널논문)
Files in This Item:
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