title: Role of osteopontin in amplification and perpetuation of rheumatoid synovitis.
abstract: Osteopontin (OPN) is an extracellular matrix protein of pleiotropic properties and has been recently recognized as a potential inflammatory cytokine. In this study, we demonstrate, for the first time to our knowledge, that overexpression of OPN in synovial T cells is associated with local inflammatory milieu and that OPN acts as an important mediator in amplification and perpetuation of rheumatoid synovitis. The study revealed that mRNA expression of OPN was highly elevated in CD4(+) synovial T cells derived from patients with RA, which correlated with increased OPN concentrations in synovial fluid (SF). The pattern of OPN overexpression was confined to rheumatoid synovium and correlated with coexpression of selected OPN receptors in synovial T cells, including integrins alphav and beta1 and CD44. RA-derived SF stimulated the expression of OPN in T cells, which was attributable to IL-10 present in SF and abrogated by anti-IL-10 antibody. Among the more than 300 autoimmune and inflammatory response genes examined, OPN selectively induced the expression of proinflammatory cytokines and chemokines known to promote migration and recruitment of inflammatory cells. Furthermore, it was evident that OPN activated transcription factor NF-kappaB in mononuclear cells. The study has important implications for understanding the role of OPN in rheumatoid synovitis and other inflammatory conditions.
authors.affiliation: Joint Immunology Laboratory of Health Science Center and Shanghai Institute of Immunology, Shanghai Second Medical University and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China.
authors.forename: Guangwu
authors.initials: G
authors.lastname: Xu
authors.forename: Hong
authors.initials: H
authors.lastname: Nie
authors.forename: Ningli
authors.initials: N
authors.lastname: Li
authors.forename: Wenxin
authors.initials: W
authors.lastname: Zheng
authors.forename: Dongqing
authors.initials: D
authors.lastname: Zhang
authors.forename: Guozhang
authors.initials: G
authors.lastname: Feng
authors.forename: Liqing
authors.initials: L
authors.lastname: Ni
authors.forename: Rong
authors.initials: R
authors.lastname: Xu
authors.forename: Jian
authors.initials: J
authors.lastname: Hong
authors.forename: Jingwu Z
authors.initials: JZ
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000276:immunology*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D053495:Osteopontin; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology; D012795:Sialoglycoproteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D013585:Synovitis / Q000276:immunology* / Q000473:pathology; D016176:T-Lymphocyte Subsets; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D011956:Receptors, Cell Surface; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D053495:Osteopontin; D016753:Interleukin-10