Work

Pure platelet-rich plasma delays intervertebral disc degeneration by activating SIRT1-mediated autophagy in nucleus pulposus cells

Year: 2025

Type: article

Abstract: BACKGROUND: Intervertebral disc degeneration (IVDD) is characterized by nucleus pulposus cells (NPCs) apoptosis and extracellular matrix (ECM) degradation. Impaired autophagy and mitochondrial dysfunction further accelerate disc degeneration. Pure platelet-rich plasma (P-PRP), enriched in growth factors and low in pro-inflammatory mediators, has shown regenerative potential. However, its mechanism of action, particularly the role of the autophagy-related SIRT1 pathway and mitochondrial homeostasis, remains unclear. METHODS: Rabbit-derived P-PRP was prepared and analyzed for cellular content and cytokine profiling. NPCs were treated with whole blood or P-PRP, and assessed for viability (CCK-8) and migration (Transwell). An IL-1β-induced degeneration model was established, and groups were treated with SIRT1 activator (SRT1720), inhibitor (EX527), P-PRP, or P-PRP + EX527. Mitochondrial membrane potential (JC-1 staining), and apoptosis (Annexin V/PI flow cytometry) were also measured. Western blotting, immunofluorescence, qPCR, and ELISA were conducted to measure the expression of SIRT1, autophagy-related proteins, and ECM-related markers. RESULTS: P-PRP promoted the viability and migration of NPCs, reduced apoptosis, and preserved ECM homeostasis in inflammatory conditions. P-PRP enhanced the expression of SIRT1, improved mitochondrial membrane potential, and reduced apoptosis rates. P-PRP upregulated LC3B-II and Beclin-1 expression, while downregulated p62 expression, indicating autophagy activation. EX-527 abrogated the beneficial effects of P-PRP. CONCLUSION: P-PRP protected against degenerative NPCs by activating functional autophagic flux and restoring mitochondrial function via the SIRT1 signaling axis. These findings provide novel mechanistic insight into PRP-based therapies and identify SIRT1 as a promising target for the treatment of IVDD.

Source: Journal of Orthopaedic Surgery and Research

DOI: 10.1186/s13018-025-06205-0

Authors: Jiaheng Han, Zhili Ding, Jie Huang, Yan Zhang, Yu Ding

Institutions: Chinese PLA General Hospital, South China University of Technology, Anhui Medical University, Peking University, Peking University People's Hospital

Language: English

Topic: Spine and Intervertebral Disc Pathology

Subfield: Pathology and Forensic Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,090