Periostin promotes nucleus pulposus cells apoptosis by activating the Wnt/β-catenin signaling pathway

Abstract

Intervertebral disc (IVD) degeneration (IVDD) is closely linked to degenerative spinal disease, resulting in disability, poor quality of life, and financial burden. Apoptosis of nucleus pulposus (NP) cells (NPCs) is a key pathological basis of IVDD. Periostin (POSTN), an extracellular matrix protein, is expressed in many tissues, whereas its abnormal expression is associated with IVDD. The conventional Wnt/β-catenin pathway is also involved in IVDD and contributes to NPCs apoptosis. However, research on the mechanisms of POSTN in IVDD is lacking. This study investigated the relationship between POSTN and β-catenin expression in degenerated IVDs. We detected the expression of POSTN, β-catenin, and cleaved-caspase-3 (C-caspase3) in degenerated and non-degenerated IVD tissues of different grades (n = 8) using RT-qPCR, immunohistochemical staining, and western blotting analysis. Next, we explored the effects of recombinant periostin (rPOSTN) and isoquercitrin (Iso), an inhibitor of the Wnt/β-catenin pathway, on NPCs apoptosis. Finally, we inhibited the expression of POSTN in degenerated NPCs in vivo and investigated the anti-apoptotic effect. The expression of β-catenin, POSTN, and C-caspase3 in severe degenerative IVDs was significantly higher than that in mild degenerative IVDs. These findings were confirmed in rat and cell-based degenerative models. When treated with rPOSTN, the Wnt/β-catenin pathway activity and cell apoptosis were time- and dose-dependent. However, rPOSTN-induced NPCs apoptosis decreased after iso-induced inhibition of the Wnt/β-catenin pathway. POSTN inhibition reduced apoptosis but was restored by rPOSTN re-addition. Lastly, POSTN inhibition ameliorated puncture-induced IVDD in vivo. Overall, our study demonstrated that POSTN promotes NPCs apoptosis and aggravates degeneration by activating the Wnt/β-catenin pathway.

Keywords: apoptosis; degeneration; intervertebral disc; mechanism; nucleus pulposus; periostin.