XB-ART-55354Sci Transl Med January 1, 2018; 10 (462):
ITGBL1 modulates integrin activity to promote cartilage formation and protect against arthritis.
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.
PubMed ID: 30305454
Article link: Sci Transl Med
Species referenced: Xenopus
Genes referenced: col2a1 itga1 itga10 itga3 itga5 itgb1 itgbl1 mmp13 mmp3 sox9
GO keywords: cartilage development
Morpholinos: itgbl1 MO1
Disease Ontology terms: osteoarthritis
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