ITGBL1 modulates integrin activity to promote cartilage formation and protect against arthritis

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Title
ITGBL1 modulates integrin activity to promote cartilage formation and protect against arthritis
Author(s)
Eun Kyung Jeon; Jimin Jeon; Dong Gil Jang; Ha Eun Kim; Hyo Jung Sim; Keun Yeong Kwon; Medina-Ruíz, Sofía; Hyun Jun Jang; Ah Reum Lee; Jun Gi Rho; Hyun Shik Lee; Seok Jung Kim; Chan Young Park; Kyungjae Myung; Wook Kim; Taejoon Kwon; Siyoung Yang; Tae Joo Park
Publication Date
2018-10
Journal
Science Translational Medicine, v.10, no.462, pp.7486 -
Publisher
AMER ASSOC ADVANCEMENT SCIENCE
Abstract
Developing and mature chondrocytes constantly interact with and remodel the surrounding extracellular matrix (ECM). Recent research indicates that integrin-ECM interaction is differentially regulated during cartilage formation (chondrogenesis). Integrin signaling is also a key source of the catabolic reactions responsible for joint destruction in both rheumatoid arthritis and osteoarthritis. However, we do not understand how chondrocytes dynamically regulate integrin signaling in such an ECM-rich environment. Here, we found that developing chondrocytes express integrin-β-like 1 (Itgbl1) at specific stages, inhibiting integrin signaling and promoting chondrogenesis. Unlike cytosolic integrin inhibitors, ITGBL1 is secreted and physically interacts with integrins to down-regulate activity. We observed that Itgbl1 expression was strongly reduced in the damaged articular cartilage of patients with osteoarthritis (OA). Ectopic expression of Itgbl1 protected joint cartilage against OA development in the destabilization of the medial meniscus-induced OA mouse model. Our results reveal ITGBL1 signaling as an underlying mechanism of protection against destructive cartilage disorders and suggest the potential therapeutic utility of targeting ITGBL1 to modulate integrin signaling in human disease. Copyright © 2018 The Authors, some rights reserved.
URI
https://pr.ibs.re.kr/handle/8788114/5121
ISSN
1946-6234
Appears in Collections:
Center for Genomic Integrity(유전체 항상성 연구단) > Journal Papers (저널논문)
Files in This Item:
2018_Sci. Trans._ITGBL1 modulates integrin activity to promote cartilage formation and protect against arthritis_Tea Joo Park.pdfDownload

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