TNF-α Regulates ITGβ1 and SYND4 Expression in Nucleus Pulposus Cells: Activation of FAK/PI3K Signaling

Integrins can function synergistically with syndecan-4 (SYND4) and bind to the fibronectin (FN) matrix, resulting in the regulation of tissue regeneration. This study aimed to explore the effects of TNF-α on the formation of FN/ITGβ1/SYND4 complex and the relative mechanism in NP cells. The expression of FN-ITG-SYND4 at the cellular level under TNF-α stimulation was detected by immunofluorescent staining, western blotting, and RT-PCR. ITGβ1 is a crucial component of ITG FN-induced FAK signaling, which was detected using dual mode. And, the involved signaling down stream pathways were also detected. FN is a preferred adhesion substrate for NP cells and that integrin β1 (ITGβ1) and SYND4 work synergistically during ECM engagement in a focal adhesion kinase (FAK)-dependent fashion. The PI3k/Akt pathway is obviously down-regulated, resulting in decreased adherence capacity and increased anoikis. TNF-α induction could weaken FAK activity and downstream levels of phospho-PI3K and Akt, resulting in decreased adherence capacity and increased apoptosis. Thus, TNF-α is essential for the formation of FN/ITGβ1/SYND4 complex in NP cells and further elucidates the inflammatory mechanism of NP cells degeneration.