title: Activation of Akt leading to NF-κB up-regulation in chondrocytes stimulated with fibronectin fragment.
abstract: Increased fibronectin fragments are thought to contribute to joint destruction in osteoarthritis (OA). However, the mechanism whereby fibronectin fragments cause catabolic activities is not totally understood. While COOH-terminal heparin-binding fibronectin fragment (HBFN-f) has been shown to activate nuclear factor (NF)-κB pathway, intracellular upstream events that cause NF-κB up-regulation in response to HBFN-f remain unclear. Thus, this study was aimed to elucidate the involvement of phosphoinositide-3-OH kinase (PI3K)/Akt pathway in NF-κB activation by HBFN-f in OA chondrocytes. In chondrocyte monolayer cultures, HBFN-f stimulated nitric oxide (NO) production in association with phosphorylation of NF-κB and Akt. Inhibition studies using LY294002 revealed the requirement of PI3K/Akt pathway for NO production and NF-κB activation by HBFN-f. Anti-CD44 treatment with anti-CD44 antibody and hyaluronan resulted in significant inhibition of HBFN-f actions on NO, NF-κB, and Akt. Herein, we provided the first evidence that HBFN-f activates PI3K/Akt pathway leading to up-regulation of NF-κB through interaction with CD44.
authors.affiliation: Department of Sports Medicine, Tenri University. tadyasu@sta.tenri-u.ac.jp
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yasuda
mesh_terms: D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D002867:Chromones / Q000494:pharmacology; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D002867:Chromones; D005353:Fibronectins; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid; D009025:Morpholines; D009569:Nitric Oxide; D010446:Peptide Fragments; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D051996:Transcription Factor RelA; C497483:CD44 protein, human; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one