TFDP1 overexpression promotes apoptosis of nucleus pulposus cells in intervertebral disc degeneration through regulating ADAM15/MMP9 axis.

Abstract

Intervertebral disc degeneration (IVDD) is a common contributor for low back pain, which is featured by loss of extracellular matrix and nucleus pulposus cells (NPCs). Hence, our current study is undertaken to explore the potential mechanism of NPC apoptosis during IVDD. Transcription factor Dp-1 (TFDP1) expression in degenerative and non-degenerative intervertebral disc tissues was analyzed by bioinformatics. After transfection as needed, viability and apoptosis of NPCs were evaluated by cell counting kit-8 assay and flow cytometry, respectively. Western blot or quantitative real-time reverse transcription polymerase chain reaction was applied to assess expressions of TFDP1, matrix metallopeptidase 9 (MMP9), a disintegrin and metalloproteinase 15 (ADAM15), and apoptosis-associated proteins. TFDP1 expression was upregulated in degenerative intervertebral disc tissues. TFDP1 overexpression repressed viability, promoted apoptosis, increased expressions of Bax, Cleaved caspase 3, MMP9 and ADAM15, and decreased Bcl-2 expression in NPCs, while TFDP1 silencing did conversely. ADAM15 silencing promoted viability, inhibited apoptosis, increased Bcl-2 expression, and decreased Bax, Cleaved caspase 3, and MMP9 expressions in NPCs, which were reversed by TFDP1 overexpression. TFDP1 overexpression promotes apoptosis of NPCs in IVDD through regulating ADAM15/MMP9 axis, highlighting its role as a molecular target for the treatment of low back pain.