BMP9 Promotes the Extracellular Matrix of Nucleus Pulposus Cells via Inhibition of the Notch Signaling Pathway.

ABSTRACT

Intervertebral disk degeneration (IDD) is a common disease that is caused by degeneration of the nucleus pulposus (NP). One goal in the treatment of IDD is delaying or reversing the degeneration of NP via the transformation of exogenous genes. This study first investigated the role of BMP9 in the extracellular matrix (ECM) of nucleus pulposus cells (NPCs) and its mechanism. We found that BMP9 promotes the expression of ECM in NPCs, and the key molecules of Notch signaling, namely, NICD-1, hes and hey, and it was significantly altered in BMP9-transfected NPCs, which suggests that BMP9 may regulate the ECM via the Notch signaling pathway. We verified the expression of Notch ligands and receptors in NPCs infected with Ad-BMP9 and demonstrated a significant decrease in DLL1 and Notch1; then, NPCs were transfected with Ad-dnNotch1, Ad-Jagged1, and Ad-DLL1, and different multiple groups were established to further identify the ligands or receptors that affected ECM expression. The results demonstrated that Ad-dnNotch1, Jagged1 and DLL1 inhibited ECM expression, and dnNotch1 promoted expression. Therefore, we demonstrated that BMP9 promoted the expression of ECM in NPCs via inhibition of Notch1 and DLL1. This study provides a possible method for IDD treatment.