title: High level of interleukin-32 gamma in the joint of ankylosing spondylitis is associated with osteoblast differentiation.
abstract: BACKGROUND
  The formation of bony spurs and ankylosis is a key pathognomic feature in ankylosing spondylitis (AS) and results in functional impairment. The aim of this study was to investigate the role of IL-32γ in osteoblast (OB) differentiation and its association with the pathogenesis of AS.
  
  
  METHODS
  The concentration and expression of IL-32γ were evaluated in synovial fluid and tissue from patients with AS, rheumatoid arthritis (RA) and osteoarthritis (OA), using enzyme-linked immunosorbent assay and immunohistochemistry. To establish whether IL-32γ affects OB differentiation, we used calvarial cells of IL-32γ transgenic (TG) mice or wild-type (WT) mice. To elucidate the mechanism of osteoblastogenesis, levels of regulators were assayed in IL-32γ TG mice and in primary OBs after IL-32γ stimulation.
  
  
  RESULTS
  The IL-32γ levels were higher in the synovial fluid of AS patients compared with RA or OA patients and the expression of IL-32 was higher in AS synovia than in RA or OA synovia. Additional IL-32γ stimulation in precursor cells enhanced OB differentiation potentially and IL-32γ TG mice showed higher rates of OB differentiation than WT mice. IL-32γ reduced the expression of DKK-1, a negative regulator, in both WT precursor cells and human OBs and the constitutive expression of DKK-1 was suppressed in calvarial cells from IL-32γ TG mice.
  
  
  CONCLUSIONS
  The elevated level of IL-32γ in AS joint could enhance OB differentiation via DKK-1 suppression. Therefore, IL-32γ might be a putative molecular target to prevent the abnormal bone formation in AS.
authors.affiliation: Department of Rheumatology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43 gil, Songpa-gu, Seoul, 05505, Korea. krys72@hanmail.net.
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Department of Biomedical Sciences, Cell Dysfunction Research Center and BMIT, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43 gil, Songpa-gu, Seoul, 05505, Korea. ejlee09@gmail.com.
authors.forename: Eun-Jin
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Department of Biomedical Sciences, Cell Dysfunction Research Center and BMIT, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43 gil, Songpa-gu, Seoul, 05505, Korea. rcn-2xx@hanmail.net.
authors.forename: Yeon-Ho
authors.initials: YH
authors.lastname: Chung
authors.affiliation: Department of Biomedical Sciences, Cell Dysfunction Research Center and BMIT, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43 gil, Songpa-gu, Seoul, 05505, Korea. astrony_@nate.com.
authors.forename: Da-Hyun
authors.initials: DH
authors.lastname: Song
authors.affiliation: Department of Rheumatology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43 gil, Songpa-gu, Seoul, 05505, Korea. hongsc97@hanmail.net.
authors.forename: Seokchan
authors.initials: S
authors.lastname: Hong
authors.affiliation: Department of Rheumatology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43 gil, Songpa-gu, Seoul, 05505, Korea. cklee@amc.seoul.kr.
authors.forename: Chang-Keun
authors.initials: CK
authors.lastname: Lee
authors.affiliation: Department of Rheumatology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43 gil, Songpa-gu, Seoul, 05505, Korea. byoo@amc.seoul.kr.
authors.forename: Bin
authors.initials: B
authors.lastname: Yoo
authors.affiliation: Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, 133-791, Korea. thkim@hanyang.ac.kr.
authors.forename: Tae-Hwan
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Department of Orthopaedic Surgery, Guri Hospital, Hanyang University College of Medicine, Kyunggi-do, 471-701, Korea. hyparkys@hanyang.ac.kr.
authors.forename: Ye-Soo
authors.initials: YS
authors.lastname: Park
authors.affiliation: Department of Biomedical Science and Technology, Konkuk University, Seoul, 143-701, Korea. soohyun@konkuk.ac.kr.
authors.forename: Soo-Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Biomedical Sciences, Cell Dysfunction Research Center and BMIT, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43 gil, Songpa-gu, Seoul, 05505, Korea. ejchang@amc.seoul.kr.
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Chang
authors.affiliation: Department of Rheumatology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43 gil, Songpa-gu, Seoul, 05505, Korea. bestmd2000@amc.seoul.kr.
authors.forename: Yong-Gil
authors.initials: YG
authors.lastname: Kim
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D007378:Interleukins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013167:Spondylitis, Ankylosing / Q000378:metabolism / Q000473:pathology*; D013582:Synovial Fluid / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism
chemical_list: C496971:IL32 protein, human; D007378:Interleukins; C569037:interleukin-32, mouse