Anti-IL-20 monoclonal antibody inhibited inflammation and protected against cartilage destruction in murine models of osteoarthritis

• Published in: PloS one 2017-04, Vol.12 (4), p.e0175802-e0175802
• Main Authors: Hsu, Yu-Hsiang, Yang, Ya-Yu, Huwang, Man-Hsiang, Weng, Yun-Han, Jou, I-Ming, Wu, Po-Tin, Lin, Tain-Yu, Wu, Li-Wha, Chang, Ming-Shi
• Format: Article
• Language: English
• Subjects: Aggrecan; Animal models; Animals; Antibodies, Monoclonal - pharmacology; Arthritis; Biochemistry; Biocompatibility; Biology and Life Sciences; Cartilage; Cartilage (articular); Cartilage diseases; Cartilage, Articular - metabolism; Cartilage, Articular - pathology; Cell Differentiation; Chemical compounds; Chondrocytes; Clinical medicine; Collagen; Collagenase 3; Cytokines; Cytokines - metabolism; Destruction; Disease Models, Animal; Enzymes; Fibroblasts; Gene expression; Hospitals; Humans; Hypoxia; Inflammation; Inflammation - metabolism; Inflammation - prevention & control; Interleukin 20; Interleukin 6; Interleukins - immunology; Interstitial collagenase; JNK protein; Knee; Male; Matrix metalloproteinase; Matrix Metalloproteinase 1 - metabolism; Matrix Metalloproteinase 13 - metabolism; Medical treatment; Medicine; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Molecular biology; Monoclonal antibodies; Monocyte chemoattractant protein 1; Orthopedics; Osteoarthritis; Osteoarthritis - genetics; Osteoarthritis - metabolism; Osteoarthritis - pathology; Pathogenesis; Pharmacology; Protein Kinases - metabolism; Rats; Rats, Sprague-Dawley; Receptors; Research and Analysis Methods; Rheumatoid arthritis; Rheumatology; Rodents; Severity of Illness Index; Stem cells; Surgery; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Western blotting
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0175802

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.