Institute of Biopharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan City 701, Taiwan.
J Exp Med. 2011 Aug 29;208(9):1849-61. doi: 10.1084/jem.20102234. Epub 2011 Aug 15.
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.
白细胞介素-20（IL-20）是一种属于白细胞介素-10 家族的促炎细胞因子，与银屑病、类风湿性关节炎、动脉粥样硬化和中风有关。然而，关于白细胞介素-20 在骨破坏中的作用知之甚少。我们研究了白细胞介素-20 在破骨细胞生成中的作用，以及抗白细胞介素-20 单克隆抗体 7E 治疗骨质疏松症的潜在治疗作用。在骨质疏松症和骨质疏松症患者以及去卵巢（OVX）小鼠中检测到更高的血清白细胞介素-20 水平。白细胞介素-20 通过上调破骨细胞前体细胞中的核因子-κB（NF-κB）受体激活剂（RANK）表达和成骨细胞中的 RANK 配体（RANKL）来介导破骨细胞生成。7E 治疗在体外完全抑制了巨噬细胞集落刺激因子（M-CSF）和 RANKL 诱导的破骨细胞分化，并在体内保护了 OVX 小鼠免受骨丢失的影响。此外，白细胞介素-20 受体 1（IL-20R1）缺陷小鼠的骨矿物质密度（BMD）明显高于野生型对照。IL-20R1 缺陷也消除了白细胞介素-20 诱导的破骨细胞生成，并增加了 OVX 小鼠的 BMD。我们已经确定白细胞介素-20 在破骨细胞分化中具有关键作用，并且我们得出结论，抗白细胞介素-20 单克隆抗体是一种潜在的治疗骨质疏松性骨丢失的方法。
