title: Reciprocal cross-talk between RANKL and interferon-gamma-inducible protein 10 is responsible for bone-erosive experimental arthritis.
abstract: OBJECTIVE
  Interferon-gamma-inducible protein 10 (IP-10; also called CXCL10), a chemokine important in the migration and proliferation of T cells, is induced in a wide variety of cell types. However, the role of IP-10 in rheumatoid arthritis (RA) remains largely unknown. The purpose of this study was to examine the potential role of IP-10 in bone resorption and RA through examination of a mouse model of collagen-induced arthritis (CIA).
  
  
  METHODS
  The effects of IP-10 on mouse T cells during osteoclast differentiation were examined in migration assays. The bone-erosive activity of IP-10 was determined in vivo in a mouse model of CIA by histologic and immunostaining analyses. Cytokine levels in serum and culture medium were measured with sandwich enzyme-linked immunosorbent assays.
  
  
  RESULTS
  Serum concentrations of IP-10 were significantly higher in mice with CIA than in control mice. RANKL greatly induced IP-10 expression in osteoclast precursors, but not in mature osteoclasts. IP-10 stimulated the expression of RANKL and tumor necrosis factor alpha (TNFalpha) in CD4+ T cells and induced osteoclastogenesis in cocultures of CD4+ T cells and osteoclast precursors. However, IP-10 did not induce RANKL or TNFalpha in CD8+ T cells. Treatment with neutralizing antibody to IP-10 significantly inhibited the infiltration of CD4+ T cells and F4/80+ macrophages into the synovium and attenuated bone destruction in mice with CIA. Furthermore, levels of RANKL and TNFalpha were inhibited by antibody to IP-10. Bone erosion was observed in mice infected with an IP-10 retrovirus.
  
  
  CONCLUSIONS
  Our findings suggest that IP-10 plays a critical role in the infiltration of CD4+ T cells and F4/80+ macrophages into inflamed joints and causes bone destruction. Our results provide the first evidence that IP-10 contributes to the recruitment of inflammatory cells and is involved in bone erosion in inflamed joints.
authors.affiliation: Wonkwang University School of Medicine, Iksan, Republic of Korea.
authors.forename: Han Bok
authors.initials: HB
authors.lastname: Kwak
authors.forename: Hyunil
authors.initials: H
authors.lastname: Ha
authors.forename: Ha-Neui
authors.initials: HN
authors.lastname: Kim
authors.forename: Jong-Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Hun Soo
authors.initials: HS
authors.lastname: Kim
authors.forename: Seungbok
authors.initials: S
authors.lastname: Lee
authors.forename: Hyun-Man
authors.initials: HM
authors.lastname: Kim
authors.forename: Jung Yeon
authors.initials: JY
authors.lastname: Kim
authors.forename: Hong-Hee
authors.initials: HH
authors.lastname: Kim
authors.forename: Yeong Wook
authors.initials: YW
authors.lastname: Song
authors.forename: Zang Hee
authors.initials: ZH
authors.lastname: Lee
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000209:etiology* / Q000276:immunology; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000502:physiology*; D051379:Mice; D008811:Mice, Inbred DBA; D053245:RANK Ligand / Q000502:physiology*
chemical_list: D054357:Chemokine CXCL10; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse