Anti-IL-20 monoclonal antibody inhibits the differentiation of osteoclasts and protects against osteoporotic bone loss

Yu Hsiang Hsu, Wei Yu Chen, Chien Hui Chan, Chih Hsing Wu, Zih Jie Sun, Ming Shi Chang

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

IL-20 is a proinflammatory cytokine of the IL-10 family that is involved in psoriasis, rheumatoid arthritis, atherosclerosis, and stroke. However, little is known about the role of IL-20 in bone destruction. We explored the function of IL-20 in osteoclastogenesis and the therapeutic potential of anti-IL-20 monoclonal antibody 7E for treating osteoporosis. Higher serum IL-20 levels were detected in patients with osteopenia and osteoporosis and in ovariectomized (OVX) mice. IL-20 mediates osteoclastogenesis by up-regulating the receptor activator of NF-κB (RANK) expression in osteoclast precursor cells and RANK ligand (RANKL) in osteoblasts. 7E treatment completely inhibited osteoclast differentiation induced by macrophage colony-stimulating factor (M-CSF) and RANKL in vitro and protected mice from OVXinduced bone loss in vivo. Furthermore, IL-20R1-deficient mice had significantly higher bone mineral density (BMD) than did wild-type controls. IL-20R1 deficiency also abolished IL-20- induced osteoclastogenesis and increased BMD in OVX mice. We have identified a pivotal role of IL-20 in osteoclast differentiation, and we conclude that anti-IL-20 monoclonal antibody is a potential therapeutic for protecting against osteoporotic bone loss.

Original languageEnglish
Pages (from-to)1849-1861
Number of pages13
JournalJournal of Experimental Medicine
Volume208
Issue number9
DOIs
Publication statusPublished - 2011 Aug 29

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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