title: Anti-IL-20 monoclonal antibody promotes bone fracture healing through regulating IL-20-mediated osteoblastogenesis.
abstract: Bone loss and skeletal fragility in bone fracture are caused by an imbalance in bone remodeling. The current challenge in bone fracture healing is to promote osteoblastogenesis and bone formation. We aimed to explore the role of IL-20 in osteoblastogenesis, osteoblast differentiation and bone fracture. Serum IL-20 was significantly correlated with serum sclerostin in patients with bone fracture. In a mouse model, anti-IL-20 monoclonal antibody (mAb) 7E increased bone formation during fracture healing. In vitro, IL-20 inhibited osteoblastogenesis by upregulating sclerostin, and downregulating osterix (OSX), RUNX2, and osteoprotegerin (OPG). IL-20R1 deficiency attenuated IL-20-mediated inhibition of osteoblast differentiation and maturation and reduced the healing time after a bone fracture. We conclude that IL-20 affects bone formation and downregulates osteoblastogenesis by modulating sclerostin, OSX, RUNX2, and OPG on osteoblasts. Our results demonstrated that IL-20 is involved in osteoregulation and anti-IL-20 mAb is a potential therapeutic for treating bone fracture or metabolic bone diseases.
authors.affiliation: Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Clinical Medicine Research Center, National Cheng Kung University Hospital, Tainan, Taiwan.
authors.forename: Yu-Hsiang
authors.initials: YH
authors.lastname: Hsu
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yi-Shu
authors.initials: YS
authors.lastname: Chiu
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Wei-Yu
authors.initials: WY
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Kuo-Yuan
authors.initials: KY
authors.lastname: Huang
authors.affiliation: Department of Orthopedics, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: I-Ming
authors.initials: IM
authors.lastname: Jou
authors.affiliation: Department of Orthopedics, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Po-Tin
authors.initials: PT
authors.lastname: Wu
authors.affiliation: Department of Family Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chih-Hsing
authors.initials: CH
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Ming-Shi
authors.initials: MS
authors.lastname: Chang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D002454:Cell Differentiation / Q000187:drug effects; D004195:Disease Models, Animal; D050723:Fractures, Bone / Q000473:pathology*; D007155:Immunologic Factors / Q000008:administration & dosage*; D007378:Interleukins / Q000037:antagonists & inhibitors*; D051379:Mice; D010006:Osteoblasts / Q000502:physiology*; D010012:Osteogenesis / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D007155:Immunologic Factors; D007378:Interleukins; C422042:interleukin 20