title: A novel histone deacetylase 6-selective inhibitor suppresses synovial inflammation and joint destruction in a collagen antibody-induced arthritis mouse model.
abstract: OBJECTIVE
  To investigate the effects of Tubastatin A, a selective histone deacetylase-6 inhibitor, on synovial inflammation and joint destruction in a collagen antibody-induced arthritis (CAIA) mouse model.
  
  
  METHODS
  Collagen antibody-induced arthritis mice were given daily intraperitoneal injections of various concentrations of Tubastatin A (0, 10, 50, 100 mg/kg). The clinical score and paw thickness were measured. Mice were sacrificed on day 15, and the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1 and IL-6 in the serum were analyzed using enyme-linked immunosorbent assay (ELISA). Two pathologists independently measured the synovitis score. Micro-computed tomography (CT) scans of the joints were performed to quantify joint destruction. The expression of IL-6 from human fibroblast-like synoviocytes (FLSs) after incubation with various doses of Tubastatin A (0, 0.75, 1.5, 3 μmol/L) was measured using ELISA.
  
  
  RESULTS
  The clinical arthritis score was significantly attenuated and paw thickness was lower in the group treated with 100 mg/kg Tubastatin A compared with those treated with vehicle alone. The synovitis score was significantly reduced in the 100 mg/kg Tubastatin A-treated group compared with the control group. Micro-CT showed that quantitative measures of joint destruction were significantly attenuated in the 100 mg/kg Tubastatin A-treated group compared with the control. The expression of IL-6 in the sera was lower in the mice treated with Tubastatin A compared with the control. The expression of IL-6 in human FLSs decreased dose-dependently after incubation with Tubastatin A without affecting cell viability.
  
  
  CONCLUSIONS
  Tubastatin A successfully ameliorated synovial inflammation and protected against joint destruction in CAIA mice, at least in part, by modulating IL-6 expression.
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jaejoon
authors.initials: J
authors.lastname: Lee
authors.affiliation: Samsung Biomedical Research Institute, Seoul, Korea.
authors.forename: Eun Chung
authors.initials: EC
authors.lastname: Hong
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hyemin
authors.initials: H
authors.lastname: Jeong
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Hwang
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hyungjin
authors.initials: H
authors.lastname: Kim
authors.affiliation: Samsung Biomedical Research Institute, Seoul, Korea.
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Bae
authors.affiliation: Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Joong Kyong
authors.initials: JK
authors.lastname: Ahn
authors.affiliation: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Yoon-La
authors.initials: YL
authors.lastname: Choi
authors.affiliation: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jungho
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hoon-Suk
authors.initials: HS
authors.lastname: Cha
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Koh
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000000981:diagnostic imaging / Q000473:pathology / Q000517:prevention & control*; D001175:Arthrography; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology* / Q000627:therapeutic use*; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007596:Joints / Q000187:drug effects / Q000473:pathology*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013585:Synovitis / Q000000981:diagnostic imaging / Q000473:pathology / Q000517:prevention & control*; D014057:Tomography, X-Ray Computed
chemical_list: D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; D007375:Interleukin-1; D015850:Interleukin-6; C553587:tubastatin A; C499033:Hdac6 protein, mouse; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases
keywords: collagen antibody-induced arthritis; erosion; rheumatoid arthritis; tubastatin