ITGBL1 modulates integrin activity to promote cartilage formation and protect against arthritis
| Autor: | Hyun-Shik Lee, Dong Gil Jang, Tae Joo Park, Ha Eun Kim, Kyungjae Myung, Ah Reum Lee, Hyo Jung Sim, Chan Young Park, Siyoung Yang, Taejoon Kwon, Keun Yeong Kwon, Eun Kyung Song, Jun Gi Rho, Seok Jung Kim, Hyun-Jun Jang, Sofia Medina-Ruiz, Wook Kim, Jimin Jeon |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Cartilage
Articular 0301 basic medicine Embryo Nonmammalian Xenopus Cartilage disorder Cellular differentiation Integrin Arthritis Osteoarthritis Extracellular matrix Mice 03 medical and health sciences Chondrocytes Cell Line Tumor medicine Animals Humans Aged biology Chemistry Integrin beta1 Cartilage Cell Differentiation Mesenchymal Stem Cells General Medicine Middle Aged Chondrogenesis medicine.disease Extracellular Matrix Cell biology Disease Models Animal 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation Face biology.protein Joints |
| Zdroj: | Science Translational Medicine. 10 |
| ISSN: | 1946-6242 1946-6234 |
| DOI: | 10.1126/scitranslmed.aam7486 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|