title: RECK is up-regulated and involved in chondrocyte cloning in human osteoarthritic cartilage.
abstract: Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) is a membrane-anchored matrix metalloproteinase regulator, but its functions in cartilage are not fully understood. The aim of the present study was to examine the expression and functions of RECK in human osteoarthritic (OA) cartilage. Quantitative RT-PCR indicated that the expression level of RECK is significantly higher in OA cartilage than in normal cartilage. By immunohistochemical analysis, RECK was localized to chondrocytes in OA cartilage, and the immunoreactivity directly correlated with the Mankin score and degree of chondrocyte cloning and proliferation. In cultured OA chondrocytes, RECK was expressed on the cell surface by glycosylphosphatidylinositol anchoring. The expression was stimulated by insulin-like growth factor-1 and suppressed by interleukin-1 and tumor necrosis factor-alpha. Down-regulation of RECK by small interfering RNA showed reduced spreading and smaller focal adhesions in the chondrocytes. Chondrocyte migration in a monolayer wounding assay was increased by down-regulation of RECK and inhibited by RECK overexpression in an matrix metalloproteinase activity-dependent manner. On the other hand, chondrocyte proliferation was suppressed by RECK silencing, and this was associated with reduced phosphorylation of focal adhesion kinase and extracellular signal-regulated kinase, whereas the proliferation was enhanced by RECK overexpression. These data are the first to demonstrate that RECK is up-regulated in human OA cartilage and suggest that RECK plays a role in chondrocyte cloning probably through suppression and promotion of chondrocyte migration and proliferation, respectively.
authors.affiliation: Department of Pathology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-0016, Japan.
authors.forename: Tokuhiro
authors.initials: T
authors.lastname: Kimura
authors.forename: Aiko
authors.initials: A
authors.lastname: Okada
authors.forename: Taku
authors.initials: T
authors.lastname: Yatabe
authors.forename: Masashi
authors.initials: M
authors.lastname: Okubo
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Toyama
authors.forename: Makoto
authors.initials: M
authors.lastname: Noda
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Okada
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002358:Cartilage, Articular / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism* / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D058851:GPI-Linked Proteins; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D058851:GPI-Linked Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C115460:RECK protein, human; D012333:RNA, Messenger
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