title: Anti-IL-20 monoclonal antibody inhibits the differentiation of osteoclasts and protects against osteoporotic bone loss.
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 OVX-induced 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.
authors.affiliation: Institute of Biopharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan City 701, Taiwan.
authors.forename: Yu-Hsiang
authors.initials: YH
authors.lastname: Hsu
authors.forename: Wei-Yu
authors.initials: WY
authors.lastname: Chen
authors.forename: Chien-Hui
authors.initials: CH
authors.lastname: Chan
authors.forename: Chih-Hsing
authors.initials: CH
authors.lastname: Wu
authors.forename: Zih-Jie
authors.initials: ZJ
authors.lastname: Sun
authors.forename: Ming-Shi
authors.initials: MS
authors.lastname: Chang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology*; D057134:Antibodies, Neutralizing / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D005260:Female; D006801:Humans; D007378:Interleukins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008875:Middle Aged; D010010:Osteoclasts / Q000378:metabolism*; D010024:Osteoporosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000096:biosynthesis / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D057134:Antibodies, Neutralizing; D007378:Interleukins; D053246:Receptor Activator of Nuclear Factor-kappa B; D018123:Receptors, Interleukin; C505686:TNFRSF11A protein, human; C505687:Tnfrsf11a protein, mouse; C492510:interleukin-20 receptor; C422042:interleukin 20