p38gamma mitogen-activated protein kinase suppresses chondrocyte production of MMP-13 in response to catabolic stimulation.

Osteoarthritis and Cartilage
David Long, Richard F Loeser

Abstract

The signaling protein p38 mitogen-activated protein kinase is required for inflammatory signaling in chondrocytes that regulates matrix metalloproteinase (MMP) production. We sought to determine the role of specific p38 isoforms in chondrocyte catabolic signaling in response to IL-1beta and fibronectin fragments (Fn-f). Human articular chondrocytes isolated from normal ankle cartilage from tissue donors or from osteoarthritic knee cartilage obtained during knee replacement were stimulated with IL-1beta or Fn-f, with or without pretreatment with p38 inhibitors (SB203580 or BIRB796) or growth factors (IGF-1 and OP-1). p38 isoform phosphorylation was measured by antibody array and immunoblotting. MMP-13 expression was measured by real-time polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and immunoblotting. Chondrocytes were transfected with plasmids expressing constitutively active (CA) p38gamma or with adenovirus expressing dominant negative (DN) p38gamma. Stimulation of chondrocytes with either IL-1beta or Fn-f led to enhanced phosphorylation of p38alpha and p38gamma, with little phosphorylation of p38beta or p38delta isoforms. p38alpha localized to the nucleus and p38gamma to the cytosol. Inhibition ...Continue Reading

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Citations

Jan 14, 2012·Rheumatology·Indira PrasadamYin Xiao
Jul 27, 2011·Current Opinion in Rheumatology·Mary B Goldring, Miguel Otero
Aug 4, 2012·Therapeutic Advances in Musculoskeletal Disease·Mary B Goldring
Dec 17, 2011·Journal of Signal Transduction·Ana Risco, Ana Cuenda
Nov 9, 2012·International Journal of Radiation Biology·Jeffrey S WilleyRichard F Loeser
Dec 29, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Fanhua WangJian Luo

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