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 α~5~β~1~, 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 α~5~β~1~ expression and phosphorylation of the ERK~1/2~. After the expression of integrin α~5~β~1~ was silenced in NP cells, the phosphorylation of ERK~1/2~ 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~1/2~ 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 α~5~β~1~ subunit, ERK, and PKC were all included in this loop. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:556–561, 2011