title: Matrix Metalloproteinase-9 Production by Immortalized Human Chondrocyte Lines.
abstract: We reported at the Keynote Forum of Immunology Summit-2015 that recombinant human (rh) TNF-α or rhIL-6 stimulated production of matrix metalloproteinase-9 (MMP-9) in the T/C28a2 and C-28/I2 human immortalized chondrocyte cell lines. Furthermore, we reported that tocilizumab (TCZ), a fully humanized monoclonal antibody which neutralizes IL-6-mediated signaling, inhibited the rhIL-6-mediated increase in the production of MMP-9. IL-6 is also a known activator of the JAK/STAT signaling pathway. In that regard, we evaluated the effect of rhIL-6 on total and phosphorylated Signal Transducer and Activator of Transcription by these chondrocyte lines which showed that whereas STAT3 was constitutively phosphorylated in T/C28a2 chondrocytes, rhIL-6 activated STAT3 in C-28/I2 chondrocytes. The finding that rhIL-6 increased the production of MMP-9 by human immortalized chondrocyte cell lines may have important implications with respect to the destruction of articular cartilage in rheumatoid arthritis and osteoarthritis. Thus, the markedly elevated level of IL-6 in rheumatoid arthritis and osteoarthritis sera and synovial fluid would be expected to generate significant MMP-9 to cause the degradation of articular cartilage extracellular matrix proteins. The finding that TCZ suppressed rhIL-6-mediated MMP-9 production suggests that TCZ, currently employed in the medical therapy of rheumatoid arthritis, could be considered as a drug for osteoarthritis.
authors.affiliation: Department of Medicine, Division of Rheumatic Diseases, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106, USA.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Malemud
authors.affiliation: Department of Medicine, Division of Rheumatic Diseases, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106, USA.
authors.forename: Evan C
authors.initials: EC
authors.lastname: Meszaros
authors.affiliation: Department of Medicine, Division of Rheumatic Diseases, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106, USA.
authors.forename: Meredith A
authors.initials: MA
authors.lastname: Wylie
authors.affiliation: Department of Reproductive Biology, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106, USA; Department of Pathology, Institute of Pathology, Case Western Reserve University, School of Medicine, University Hospitals Case Medical Center, Cleveland, Ohio 44106, USA.
authors.forename: Wissam
authors.initials: W
authors.lastname: Dahoud
authors.affiliation: Department of Reproductive Biology, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106, USA.
authors.forename: Yelenna
authors.initials: Y
authors.lastname: Skomorovska-Prokvolit
authors.affiliation: Department of Reproductive Biology, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106, USA.
authors.forename: Sam
authors.initials: S
authors.lastname: Mesiano
keywords: Chondrocytes; Human; Matrix metalloproteinases; Osteoarthritis; Pro-inflammatory cytokines; Rheumatoid arthritis; Signal transduction