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

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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

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Osteoclasts
Monoclonal Antibodies
Bone and Bones
Osteogenesis
RANK Ligand
Bone Density
Osteoporosis
interleukin 20
Macrophage Colony-Stimulating Factor
Metabolic Bone Diseases
Osteoblasts
Psoriasis
Interleukin-10
Rheumatoid Arthritis
Atherosclerosis
Therapeutics
Stroke
Cytokines
Serum

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

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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.",
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AU - Chen, Wei Yu

AU - Chan, Chien Hui

AU - Wu, Chih-Hsing

AU - Sun, Zih-Jie

AU - Chang, Ming-Shi

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