POSTN knockdown suppresses IL-1β-induced inflammation and apoptosis of nucleus pulposus cells via inhibiting the NF-κB pathway and alleviates intervertebral disc degeneration

Abstract

The aim of this study is to investigate the effects of POSTN on IL-1β induced inflammation, apoptosis, NF-κB pathway and intervertebral disc degeneration (IVDD) in Nucleus pulposus (NP) cells (NPCs). NP tissue samples with different Pfirrmann grades were collected from patients with different degrees of IVDD. Western blot and immunohistochemical staining were used to compare the expression of POSTN protein in NP tissues. Using the IL-1β-induced IVDD model, NPCs were transfected with lentivirus-coated si-POSTN to down-regulate the expression of POSTN and treated with CU-T12-9 to evaluate the involvement of NF-κB pathway. Western blot, immunofluorescence, and TUNEL staining were used to detect the expression changes of inflammation, apoptosis and NF-κB pathway-related proteins in NPCs. To investigate the role of POSTN in vivo, a rat IVDD model was established by needle puncture of the intervertebral disc. Rats were injected with lentivirus-coated si-POSTN, and H&E staining and immunohistochemical staining were performed. POSTN expression is positively correlated with the severity of IVDD in human. POSTN expression was significantly increased in the IL-1β-induced NPCs degeneration model. Downregulation of POSTN protects NPCs from IL-1β-induced inflammation and apoptosis. CU-T12-9 treatment reversed the protective effect of si-POSTN on NPCs. Furthermore, lentivirus-coated si-POSTN injection partially reversed NP tissue damage in the IVDD model in vivo. POSTN knockdown reduces inflammation and apoptosis of NPCs by inhibiting NF-κB pathway, and ultimately prevents IVDD. Therefore, POSTN may be an effective target for the treatment of IVDD.