POSTN promotes nucleus pulposus cell senescence and extracellular matrix metabolism via activing Wnt/p-catenin and NF-cB signal pathway in intervertebral disc degeneration

Background: Intervertebral disc (IVD) degeneration (IVDD) is a prevalent condition contributing to back pain and disability. Periostin (POSTN) has emerged as a potential molecular marker and therapeutic target in IVDD, prompting further investigation into its role and mechanisms. Methods: This study employs bioinformatics analysis combined with experimental validation to explore the role of POSTN in IVDD. Gene expression datasets from the GEO database were analyzed to identify genes associated with IVDD, and the effects of POSTN on rat nucleus pulposus (NP) cells senescence and extracellular matrix (ECM) metabolism were assessed both in vitro and in vivo. Results: Elevated POSTN expression was observed in degenerated discs from IVDD patients, correlating with disease severity. In vitro experiments demonstrated that POSTN promotes NP cells senescence and ECM metabolism in a dose- and time-dependent manner. In vivo studies confirmed that POSTN inhibition can ameliorate the progression of IVDD. Further mechanistic insights revealed that POSTN may exert its effects by activating the NF- c B and Wnt/ p -catenin signaling pathways. Conclusion: POSTN plays a significant role in the pathogenesis of IVDD, with its upregulated expression closely linked to NP cells senescence and ECM metabolism. Targeting POSTN could offer a novel therapeutic strategy for IVDD. Additionally, the study predicts small molecules that may inhibit POSTN expression, providing potential candidates for the development of new drug treatments.