title: Psoriatic inflammation facilitates the onset of arthritis in a mouse model.
abstract: Psoriatic arthritis (PsA) is a seronegative, inflammatory joint disease associated with psoriasis. In most patients with PsA, skin lesions precede arthritis; however, the causality of skin inflammation for the development of arthritis remains unclear. Gp130F759/F759 knock-in (F759) mice develop autoimmune arthritis after 1 year of age through persistent signal transducer and activator of transcription 3 (Stat3) activation due to impairment in SOCS3-dependent negative regulation. Here, we crossed F759 mice with K5.Stat3C transgenic mice, in which keratinocytes express constitutive active Stat3 (Stat3C), leading to generation of psoriasis-like skin change. F759 mice harboring the K5.Stat3C transgene not only had aggravated skin lesions but also spontaneously developed arthritis with high penetrance in adjacent paws as early as 3 weeks of age. The joint lesions included swelling of the peripheral paws and nail deformities contiguous with the skin lesions, closely resembling PsA. Histopathologic study revealed enthesitis and bone erosions, with mononuclear cell infiltrates. Quantitative reverse transcriptase-PCR (RT-PCR), immunohistochemical analyses, and flow cytometry showed upregulation of the IL-23/T helper type 17 (Th17) pathway in affected joints. Furthermore, enforced generation of psoriasis-like skin inflammation by topical treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) in F759 mice induced swelling of the underlying joints. This animal model renders psoriatic inflammation as the driver of arthritis and helps to further understand the pathogenesis of PsA.
authors.affiliation: Department of Dermatology, Kochi Medical School, Kochi University, Nankoku, Japan.
authors.forename: Mayuko
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Department of Dermatology, Kochi Medical School, Kochi University, Nankoku, Japan.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Nakajima
authors.affiliation: Department of Dermatology, Kochi Medical School, Kochi University, Nankoku, Japan.
authors.forename: Mikiro
authors.initials: M
authors.lastname: Takaishi
authors.affiliation: Department of Dermatology, Graduate School of Medicine, Osaka University, Suita, Japan.
authors.forename: Shun
authors.initials: S
authors.lastname: Kitaba
authors.affiliation: Department of Molecular Imaging, Applied Medical Photonics Laboratory, Medical Photonics Research Center, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Magata
authors.affiliation: Science Research Center, Kochi University, Nankoku, Japan.
authors.forename: Sayo
authors.initials: S
authors.lastname: Kataoka
authors.affiliation: Department of Dermatology, Kochi Medical School, Kochi University, Nankoku, Japan. Electronic address: sano.derma@kochi-u.ac.jp.
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Sano
mesh_terms: D000818:Animals; D015535:Arthritis, Psoriatic / Q000209:etiology*; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D007249:Inflammation / Q000150:complications*; D007592:Joint Diseases / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011565:Psoriasis / Q000150:complications* / Q000276:immunology / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000502:physiology; D012871:Skin Diseases / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D058504:Th17 Cells / Q000276:immunology
chemical_list: D016207:Cytokines; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D013755:Tetradecanoylphorbol Acetate