2. Academic Validation
  3. Fibro-NPC: a pathogenic subtype identified at single-cell resolution with secreted SFRP4 as a biomarker in intervertebral disc degeneration

Fibro-NPC: a pathogenic subtype identified at single-cell resolution with secreted SFRP4 as a biomarker in intervertebral disc degeneration

  • J Transl Med. 2025 Aug 6;23(1):867. doi: 10.1186/s12967-025-06798-4.
Yili Xu # 1,  Zuozhi Xie # 2,  Shubo Gu # 2,  Xiang Zhao 3,  Di Zhao 4,  Zhengzheng Wu 2,  Jinfeng Wang 1,  Tao Xu 2,  Ruxue Xu 5,  Zhenhua Feng 2,  Yong Qiu 2,  Zezhang Zhu 2,  Yang Yu 2,  Bo Shi 6,  Jun Jiang 7 8
Affiliations

Affiliations

  • 1 Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Clinical College of Nanjing University of Chinese Medicine, Nanjing, 210008, China.
  • 2 Division of Spine Surgery, Department of Orthopedic Surgery, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, China.
  • 3 Department of Surgery of Spine and Spinal Cord, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Henan, 453003, Zhengzhou, China.
  • 4 Department of Ultrasound, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, 21008, China. wtongyu0618@163.com.
  • 5 School of Clinical Medicine, Bengbu Medical University, Bengbu, 233000, Anhui, China.
  • 6 Division of Spine Surgery, Department of Orthopedic Surgery, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, China. jmsshitou@163.com.
  • 7 Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Clinical College of Nanjing University of Chinese Medicine, Nanjing, 210008, China. spine821107@163.com.
  • 8 Division of Spine Surgery, Department of Orthopedic Surgery, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, China. spine821107@163.com.
  • # Contributed equally.
PMID: 40770348 DOI: 10.1186/s12967-025-06798-4
Abstract

Background: Intervertebral disc degeneration (IDD) is a primary cause of low back pain and, in severe cases, can lead to disability. Current treatments for low back pain remain limited in efficacy, underscoring the need for a deeper understanding of the molecular mechanisms driving IDD. The degeneration process is primarily driven by an imbalance in the extracellular matrix, largely due to the senescence of nucleus pulposus cells (NPCs).

Methods: Through single-cell Sequencing of degenerated nucleus pulposus tissue from five intervertebral discs, we identified five distinct NPC subtypes. Notably, fibrosis-associated NPCs (Fibro-NPC) were predominantly observed at the terminal stage of cell differentiation, identifying Fibro-NPC as a pathogenic subtype in IDD. To further explore intercellular interactions, we used the CellChat algorithm to construct a cell communication network encompassing the diverse cell types in the nucleus pulposus. Mass spectrometry analysis of normal and degenerated tissue subsequently identified seven core proteins associated with IDD. Among these, WGCNA and machine learning highlighted SFRP4 as a central pathogenic protein, highly expressed in Fibro-NPC.

Results: Advanced differentiation of nucleus pulposus cells, particularly the Fibro-NPC subtype, is associated with the secretion of SFRP4, which accelerates cellular senescence. This senescence contributes to fibrosis within the nucleus pulposus, along with angiogenesis and inflammatory infiltration in the nucleus pulposus microenvironment. Collectively, these processes drive intervertebral disc degeneration.

Conclusions: Our findings position SFRP4 as a biomarker for IDD, presenting a novel target for its diagnosis and treatment.

Keywords

Intervertebral disc degeneration; Label-free quantitative proteomics; Nucleus pulposus; Senescence; Single-cell sequencing.

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