title: Systemic neutralization of TGF-β attenuates osteoarthritis.
abstract: Osteoarthritis (OA) is a major source of pain and disability worldwide with no effective medical therapy due to poor understanding of its pathogenesis. Transforming growth factor β (TGF-β) has been reported to play a role in subchondral bone pathology and articular cartilage degeneration during the progression of OA. In this study, we demonstrated that systemic use of a TGF-β-neutralizing antibody (1D11) attenuates OA progression by targeting subchondral bone pathological features in rodent OA models. Systemic administration of 1D11 preserves the subchondral bone microarchitecture, preventing articular cartilage degeneration by inhibition of excessive TGF-β activity, in both subchondral bone and the circulation. Moreover, the aberrant increases in the numbers of blood vessels, nestin(+) mesenchymal stromal/stem cells, and osterix(+) osteoblast progenitors were normalized by 1D11 systemic injection. Thus, systemic neutralization of excessive TGF-β ligands effectively prevented OA progression in animal models, with promising clinical implications for OA treatment.
authors.affiliation: Department of Orthopaedic Surgery, Institute for Cell Engineering, Johns Hopkins University, Baltimore, Maryland.|State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Xie
authors.affiliation: Department of Orthopaedic Surgery, Institute for Cell Engineering, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Francis
authors.initials: F
authors.lastname: Tintani
authors.affiliation: Department of Orthopaedic Surgery, Institute for Cell Engineering, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Orthopaedic Surgery, Institute for Cell Engineering, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Fengfeng
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Orthopaedic Surgery, Institute for Cell Engineering, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Gehua
authors.initials: G
authors.lastname: Zhen
authors.affiliation: Department of Orthopaedic Surgery, Institute for Cell Engineering, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Tao
authors.initials: T
authors.lastname: Qiu
authors.affiliation: Department of Orthopaedic Surgery, Institute for Cell Engineering, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Mei
authors.initials: M
authors.lastname: Wan
authors.affiliation: Department of Orthopaedic Surgery, Institute for Cell Engineering, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Janet
authors.initials: J
authors.lastname: Crane
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China. qmchen@scu.edu.cn.
authors.forename: Qianming
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Orthopaedic Surgery, Institute for Cell Engineering, Johns Hopkins University, Baltimore, Maryland. xcao11@jhmi.edu.
authors.forename: Xu
authors.initials: X
authors.lastname: Cao
mesh_terms: D000818:Animals; D000070598:Anterior Cruciate Ligament Injuries / Q000188:drug therapy / Q000473:pathology; D057134:Antibodies, Neutralizing / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology; D002356:Cartilage / Q000187:drug effects / Q000473:pathology; D018450:Disease Progression; D007267:Injections; D008810:Mice, Inbred C57BL; D009500:Neutralization Tests; D010003:Osteoarthritis / Q000188:drug therapy* / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D016212:Transforming Growth Factor beta
keywords: TGF-β; antibody; cartilage; osteoarthritis; subchondral bone
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