Periostin interaction with discoidin domain receptor-1 (DDR1) promotes cartilage degeneration
| Autor: | Paolo Mignatti, Tianzhen Han, Steven B. Abramson, Mukundan Attur |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Cartilage
Articular Male 0301 basic medicine Adenoviruses Osteoarthritis Pathology and Laboratory Medicine Extracellular matrix Mice Cell Signaling Skeletal Joints Animal Cells Medicine and Health Sciences Musculoskeletal System WNT Signaling Cascade Cells Cultured Connective Tissue Cells Mice Knockout Multidisciplinary Chemistry Synovial Membrane Middle Aged Signaling Cascades Cell biology medicine.anatomical_structure ADAMTS4 Connective Tissue Medical Microbiology Viral Pathogens Viruses Medicine Female Anatomy Cellular Types Pathogens Cartilage Diseases Research Article Signal Transduction Signal Inhibition Science Surgical and Invasive Medical Procedures Periostin Microbiology 03 medical and health sciences Chondrocytes Musculoskeletal System Procedures Rheumatology Discoidin Domain Receptor 1 Matrix Metalloproteinase 13 medicine Animals Humans Microbial Pathogens Protein kinase B Aged DDR1 Joint Replacement Surgery 030102 biochemistry & molecular biology Arthritis Cartilage Organisms Biology and Life Sciences Cell Biology medicine.disease Mice Inbred C57BL Biological Tissue 030104 developmental biology DNA viruses Cell Adhesion Molecules Discoidin domain |
| Zdroj: | PLoS ONE, Vol 15, Iss 4, p e0231501 (2020) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Osteoarthritis (OA) is characterized by progressive loss of articular cartilage accompanied by the new bone formation and, often, a synovial proliferation that culminates in pain, loss of joint function, and disability. However, the cellular and molecular mechanisms of OA progression and the relative contributions of cartilage, bone, and synovium remain unclear. We recently found that the extracellular matrix (ECM) protein periostin (Postn, or osteoblast-specific factor, OSF-2) is expressed at high levels in human OA cartilage. Multiple groups have also reported elevated expression of Postn in several rodent models of OA. We have previously reported that in vitro Postn promotes collagen and proteoglycan degradation in human chondrocytes through AKT/β-catenin signaling and downstream activation of MMP-13 and ADAMTS4 expression. Here we show that Postn induces collagen and proteoglycan degradation in cartilage by signaling through discoidin domain receptor-1 (DDR1), a receptor tyrosine kinase. The genetic deficiency or pharmacological inhibition of DDR1 in mouse chondrocytes blocks Postn-induced MMP-13 expression. These data show that Postn is signaling though DDR1 is mechanistically involved in OA pathophysiology. Specific inhibitors of DDR1 may provide therapeutic opportunities to treat OA. |
| Databáze: | OpenAIRE |
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