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Anti-IL-20 monoclonal antibody inhibited inflammation and protected against cartilage destruction in murine models of osteoarthritis
Anti-IL-20 monoclonal antibody inhibited inflammation and protected against cartilage destruction in murine models of osteoarthritis
- Source :
- PLoS ONE, Vol 12, Iss 4, p e0175802 (2017), PLoS ONE
- Publication Year :
- 2017
- Publisher :
- Public Library of Science (PLoS), 2017.
-
Abstract
- Osteoarthritis (OA) is a degenerative joint disease characterized by progressive destruction of articular cartilage. Interleukin (IL)-20 is a proinflammatory cytokine involved in the pathogenesis of rheumatoid arthritis. We investigated the role of IL-20 in OA and evaluated whether anti-IL-20 antibody (7E) treatment attenuates disease severity in murine models of surgery-induced OA. Immunohistochemical staining was used to detect IL-20 and its receptors expression in synovial tissue and cartilage from OA patients, and in OA synovial fibroblasts (OASFs) and chondrocytes (OACCs) from rodents with surgery-induced OA. RTQ-PCR and western blotting were used to determine IL-20-regulated OA-associated gene expression in OASFs and OACCs. OA rats and OA mice were treated with 7E. Arthritis severity was determined based on the degree of cartilage damage and the arthritis severity score. We found that IL-20 and its receptors were expressed in OASFs and OACCs. IL-20 induced TNF-α, IL-1β, MMP-1, and MMP-13 expression by activating ERK-1/2 and JNK signals in OASFs. IL-20 not only upregulated MCP-1, IL-6, MMP-1, and MMP-13 expression, but also downregulated aggrecan, type 2 collagen, TGF-β, and BMP-2 expression in OACCs. Arthritis severity was significantly lower in 7E-treated OA rats, and 7E- or MSC-treated OA mice. Therefore, we concluded that IL-20 was involved in the progression and development of OA through inducing proinflammatory cytokines and OA-associated gene expression in OASFs and OACCs. 7E reduced the severity of arthritis in murine models of surgery-induced OA. Our findings provide evidence that IL-20 is a novel target and that 7E is a potential therapeutic agent for OA.
- Subjects :
- 0301 basic medicine
Cartilage, Articular
Male
Physiology
Arthritis
lcsh:Medicine
Osteoarthritis
Knee Joints
Biochemistry
Severity of Illness Index
Rats, Sprague-Dawley
Mice
0302 clinical medicine
Animal Cells
Immune Physiology
Medicine and Health Sciences
Medicine
lcsh:Science
Musculoskeletal System
Connective Tissue Cells
Innate Immune System
Multidisciplinary
Messenger RNA
Interleukin
Antibodies, Monoclonal
Cell Differentiation
Animal Models
Nucleic acids
medicine.anatomical_structure
Experimental Organism Systems
Connective Tissue
Rheumatoid arthritis
Cytokines
medicine.symptom
Anatomy
Cellular Types
Matrix Metalloproteinase 1
Research Article
Immunology
Inflammation
Mouse Models
Surgical and Invasive Medical Procedures
Research and Analysis Methods
Proinflammatory cytokine
03 medical and health sciences
Chondrocytes
Model Organisms
Rheumatology
Matrix Metalloproteinase 13
Animals
Humans
Aggrecan
030203 arthritis & rheumatology
business.industry
Cartilage
Interleukins
lcsh:R
Biology and Life Sciences
Cell Biology
Molecular Development
medicine.disease
Rats
Mice, Inbred C57BL
Joints (Anatomy)
Disease Models, Animal
030104 developmental biology
Biological Tissue
Immune System
RNA
lcsh:Q
business
Protein Kinases
Developmental Biology
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 12
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....03d010e7ba071a7365b901331eb5b51b