2. Academic Validation
  3. Pure platelet-rich plasma delays intervertebral disc degeneration by activating SIRT1-mediated autophagy in nucleus pulposus cells

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

  • J Orthop Surg Res. 2025 Aug 22;20(1):786. doi: 10.1186/s13018-025-06205-0.
Jiaheng Han # 1 2,  Zhili Ding # 2 3,  Jie Huang 4,  Yan Zhang 5 6,  Yu Ding 7 8 9
Affiliations

Affiliations

  • 1 Department of Orthopaedics, School of Medicine, South China University of Technology, Guangzhou, 51006, China.
  • 2 Orthopedics of TCM Senior Department, The Sixth Medical Center of PLA General Hospital, Beijing, 100048, China.
  • 3 Navy Clinical College, Fifth School of Clinical Medicine, Anhui Medical University, Hefei, China.
  • 4 Department of Spinal Surgery, Peking University People's Hospital, Peking University, Beijing, 100044, China.
  • 5 Orthopedics of TCM Senior Department, The Sixth Medical Center of PLA General Hospital, Beijing, 100048, China. zhangyan0718@163.com.
  • 6 Navy Clinical College, Fifth School of Clinical Medicine, Anhui Medical University, Hefei, China. zhangyan0718@163.com.
  • 7 Department of Orthopaedics, School of Medicine, South China University of Technology, Guangzhou, 51006, China. cosmos_dingyu@163.com.
  • 8 Orthopedics of TCM Senior Department, The Sixth Medical Center of PLA General Hospital, Beijing, 100048, China. cosmos_dingyu@163.com.
  • 9 Navy Clinical College, Fifth School of Clinical Medicine, Anhui Medical University, Hefei, China. cosmos_dingyu@163.com.
  • # Contributed equally.
PMID: 40846953 DOI: 10.1186/s13018-025-06205-0
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.

Keywords

Autophagy; Intervertebral disc degeneration; Pure platelet-rich plasma; SIRT1.

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