title: Molecular pathways involved in synovial cell inflammation and tumoral proliferation in diffuse pigmented villonodular synovitis.
abstract: Diffuse-type tenosynovial giant cell tumors, also known as pigmented villonodular synovitis, are unique mesenchymal lesions that arise from the synovial tissue of the joints. They are predominantly intraarticular, aggressive, infiltrative processes, characterized by both inflammatory or neoplastic properties and local destructive progression. The pattern of synovial gene and protein expressions in pigmented villonodular synovitis, similar to those in activated macrophages in rheumatoid arthritis, and the phenotype of multinucleated giant cells, characteristic of osteoclasts, suggest that there is a common autocrine mechanism in osteoclast differentiation in both diseases and indicate the potential utility of tumor necrosis factor (TNF)-alpha blockade. High synovial colony stimulating factor 1 (CSF1) messenger RNA (m RNA) expression in pigmented villonodular synovitis, unrelated to a chromosomal translocation involving CSF1 locus, may indicate that there is a synergic paracrine loop mediated by TNF-alpha and CSF1, as shown in both inflammatory and neoplastic conditions. The effects of a new therapeutic approach consisting in intraarticular TNF-alpha blockade were studied in four pigmented villonodular synovitis knees. Knee injections produced a rapid reduction in clinical and sonographic indexes and immunohistological alterations, confirmed by arthroscopic synovectomy. A delayed relapse in one of the four knees and unaltered synovial CSF1 expression were other important findings. In the light of these observations, CSF1/CSF1R interaction probably represents a more sensible therapeutic target than TNF-alpha blockade in the diffuse form of pigmented villonodular synovitis.
authors.affiliation: Unit of Rheumatology, Department of Clinical and Experimental Medicine, University of Padova, Padova, Italy. ugo.fiocco@unipd.it
authors.forename: U
authors.initials: U
authors.lastname: Fiocco
authors.forename: P
authors.initials: P
authors.lastname: Sfriso
authors.forename: F
authors.initials: F
authors.lastname: Lunardi
authors.forename: E
authors.initials: E
authors.lastname: Pagnin
authors.forename: F
authors.initials: F
authors.lastname: Oliviero
authors.forename: E
authors.initials: E
authors.lastname: Scagliori
authors.forename: L
authors.initials: L
authors.lastname: Cozzi
authors.forename: M
authors.initials: M
authors.lastname: Vezzù
authors.forename: B
authors.initials: B
authors.lastname: Molena
authors.forename: A
authors.initials: A
authors.lastname: Scanu
authors.forename: C
authors.initials: C
authors.lastname: Panziera
authors.forename: R
authors.initials: R
authors.lastname: Nardacchione
authors.forename: L
authors.initials: L
authors.lastname: Rubaltelli
authors.forename: J M
authors.initials: JM
authors.lastname: Dayer
authors.forename: F
authors.initials: F
authors.lastname: Calabrese
authors.forename: L
authors.initials: L
authors.lastname: Punzi
mesh_terms: D000328:Adult; D001168:Arthritis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003239:Connective Tissue Cells; D005260:Female; D015870:Gene Expression; D005870:Giant Cell Tumors / Q000276:immunology / Q000473:pathology; D015726:Giant Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007719:Knee Joint / Q000473:pathology; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction; D013582:Synovial Fluid / Q000378:metabolism; D013583:Synovial Membrane / Q000276:immunology* / Q000473:pathology*; D013586:Synovitis, Pigmented Villonodular / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor