title: Fibronectin fragment activation of ERK increasing integrin α₅ and β₁ subunit expression to degenerate nucleus pulposus cells.
abstract: Fibronectin fragments (Fn-f), which are the breakdown products of fibronectin, accumulate in the disc during degeneration and are proved to induce the degeneration of intervertebral disc. The goal of this investigation was to determine the functional role of integrin α₅ β₁, extracellular signal-regulated kinase (ERK), and protein kinase C (PKC) in the process of Fn-f degeneration nucleus pulposus (NP) cells. We found that Fn-f (100 nM, 30 kDa) exposure led to degeneration of NP cells, up-regulation of integrin α₅ β₁ expression and phosphorylation of the ERK(½) . After the expression of integrin α₅ β₁ was silenced in NP cells, the phosphorylation of ERK(½) and the expression of MMP9, MMP13, and collagen II had no difference with control under the treatment of Fn-f. Finally, when the inhibitor of ERK(½) and the inhibitor of PKC were added into the medium of NP cells; we found these two inhibitors could eliminate the effect of Fn-f on NP cells. It is concluded that Fn-f had the potential to enhance the NP cell degeneration in a vicious circle. And the integrin α₅ β₁ subunit, ERK, and PKC were all included in this loop.
authors.affiliation: Department of Orthopaedics, The First Hospital of China Medical University, Heping District, Shenyang, PR China.
authors.forename: Maosheng
authors.initials: M
authors.lastname: Xia
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhu
mesh_terms: D000328:Adult; D002102:Cadaver; D002478:Cells, Cultured; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D005353:Fibronectins / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D020868:Gene Silencing; D006801:Humans; D039081:Integrin alpha5beta1 / Q000235:genetics / Q000378:metabolism*; D007403:Intervertebral Disc / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D055959:Intervertebral Disc Degeneration / Q000378:metabolism / Q000473:pathology*; D008159:Lumbar Vertebrae / Q000473:pathology*; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction
chemical_list: D024043:Collagen Type II; D005353:Fibronectins; D039081:Integrin alpha5beta1; D010446:Peptide Fragments; D034741:RNA, Small Interfering; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D053509:Matrix Metalloproteinase 13; D020780:Matrix Metalloproteinase 9