Response of young, aged and ostheoarthritic human articular chondrocytes to inflammatory cytokines: molecular and cellular aspects (Articolo in rivista)

Type
Label
  • Response of young, aged and ostheoarthritic human articular chondrocytes to inflammatory cytokines: molecular and cellular aspects (Articolo in rivista) (literal)
Anno
  • 2002-01-01T00:00:00+01:00 (literal)
Alternative label
  • Dozin B.1, Malpeli M.1, Camardella L.2, Cancedda R.3, Pietrangelo A.4 (2002)
    Response of young, aged and ostheoarthritic human articular chondrocytes to inflammatory cytokines: molecular and cellular aspects
    in Matrix biology (Print)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Dozin B.1, Malpeli M.1, Camardella L.2, Cancedda R.3, Pietrangelo A.4 (literal)
Pagina inizio
  • 449 (literal)
Pagina fine
  • 459 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#altreInformazioni
  • In questo lavoro è stato applicato un approccio proteomico, teso ad identificare proteine che possono essere coinvolte in importanti processi dello sviluppo cellulare. Impact Factor 3.125. (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 21 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#descrizioneSinteticaDelProdotto
  • Sono state investigate le proprietà metaboliche di condrociti articolari umani derivanti da soggetti giovani, anziani e osteoartritici, in seguito al trattamento con un agente infiammatorio, in presenza e in assenza di diacereina, un potenziale farmaco da utilizzare nelle osteoartriti. Condrociti da colture primarie sono stati analizzati per la secrezione di proteine, l’attività di metallo-proteasi e la produzione di ossido nitrico. A seconda dell’età e dello stato fisiopatologico, i condrociti secernono varie proteine, identificate mediante “micro-sequencing”. In seguito ad esposizione ad agenti infiammatori, aumenta la secrezione di stromelisina, collagenasi interstiziale, interleuchina-6 e interleuchina-8, mentre non è influenzata la secrezione della proteina chitinasi-simile. La diacereina, a concentrazioni terapeutiche, contrasta l’effetto delle citochine. Questi dati dimostrano che le citochine inducono la produzione di varie proteine coinvolte nel rimodellamento della matrice cartilaginea, e che la diacereina previene queste alterazioni metaboliche, probabilmente bloccando alcuni mediatori intracellulari, come i radicali di ossigeno. (literal)
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • 1 Ist. Nazionale Ricerca sul Cancro Genova, 2 CNR, 3 Uni Genova, 4 Uni Modena e Reggio Emilia (literal)
Titolo
  • Response of young, aged and ostheoarthritic human articular chondrocytes to inflammatory cytokines: molecular and cellular aspects (literal)
Abstract
  • The aim of this study was to investigate the metabolic properties of human articular chondrocytes derived from young, aged and osteoarthritic subjects and their genetic adaptation to a catabolic challenge (i.e. the inflammatory cytokines interleukin-1alpha and tumor necrosis factor-alpha), in the absence or presence of diacerein, a drug potentially useful in osteoarthritis. Chondrocytes in primary culture were analyzed for newly secreted proteins, metalloproteinase synthesis and activity, and production of nitric oxide by-products. Results show that chondrocytes from normal but aged subjects present biochemical properties closer to osteoarthritic-derived cartilage than to normal young cartilage, as indicated by cell morphology, cell proliferation rate and pattern of protein secretion (in particular stromelysin-1 and interstitial collagenase). According to patient age and cartilage physiopathology, chondrocytes secrete increasing amounts of a protein identified by micro-sequencing as chitinase-like protein. Upon exposure to the inflammatory cytokines, chondrocytes, regardless the age or the status of the donor, significantly enhance their production of stromelysin-1, interstitial collagenase, interleukin-6 and interleukin-8. By contrast, the chitinase-like protein is not modulated by the cytokines. The pattern of protein secretion and metalloproteinase activity in chondrocytes from aged subjects appeared to be different from that of young patients, but was highly expressed in osteoarthritic chondrocytes. Diacerein, at therapeutically useful concentrations, consistently counteracts the stimulatory effect of cytokines on newly secreted proteins, metalloproteinase activity and nitric oxide production, whereas a selective nitric oxide blocker alone is ineffective. These data demonstrate that a specific gene program is turned on in cytokine-stimulated chondrocytes, which involves production of proteins engaged in remodeling and destruction of cartilage matrix. Part of these mechanisms appears to be operative also in unstimulated aged chondrocytes. Diacerein largely prevents the metabolic alterations caused by cytokine exposure in human chondrocytes, possibly through its ability to block early intracellular mediators after cytokine stimulation, such as oxygen radicals. (literal)
Prodotto di
Autore CNR
Insieme di parole chiave

Incoming links:


Autore CNR di
Prodotto
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi
Insieme di parole chiave di
data.CNR.it