GPNMB+ macrophages promote osteogenic differentiation of nucleus pulposus cells through PDGF signaling in intervertebral disc degeneration

  • Cell Rep Med. 2026 Jun 25:102886. doi: 10.1016/j.xcrm.2026.102886.
Jialin Jiang  1 ,  Fanqi Kong  2 ,  Bing Zheng  1 ,  Zijian Mei  1 ,  Jian Zhu  1 ,  Ximing Xu  1 ,  Weicheng Pan  1 ,  Ziran Wang  1 ,  Xiaofei Sun  1 ,  Kaiqiang Sun  1 ,  Le Huan  1 ,  Jiangang Shi  3 ,  Huji Xu  4 ,  Yongfei Guo  5
Affiliations
  • 1. Department of Orthopedic Surgery, Spine Center, Changzheng Hospital, Naval Medical University, Shanghai, China.
  • 2. Department of Orthopedic Surgery, Spine Center, Changzheng Hospital, Naval Medical University, Shanghai, China; Department of Orthopedic Surgery, Orthopedic Institute, The First Affiliated Hospital of SooChow University, Suzhou, China.
  • 3. Department of Orthopedic Surgery, Spine Center, Changzheng Hospital, Naval Medical University, Shanghai, China. Electronic address: [email protected].
  • 4. Department of Rheumatology and Immunology, National Key Laboratory for Immunity and Inflammation, Changzheng Hospital, Naval Medical University, Shanghai, China; Peking-Tsinghua Center for Life Sciences, Tsinghua University, Beijing, China. Electronic address: [email protected].
  • 5. Department of Orthopedic Surgery, Spine Center, Changzheng Hospital, Naval Medical University, Shanghai, China. Electronic address: [email protected].
PMID: 42349413 DOI: 10.1016/j.xcrm.2026.102886
Abstract

Phenotypic transitions of nucleus pulposus (NP) cells are increasingly recognized as key drivers of intervertebral disc degeneration (IVDD), yet the differentiation fate of NP cells and its regulation by the immune microenvironment remain unclear. Using single-cell transcriptomic profiling with in vivo and in vitro validation, we identify an osteoblast-like NP cell subpopulation that emerges during IVDD and exhibits enhanced osteogenic differentiation capacity. Genetic disruption of NP cell osteogenic potential attenuates disc degeneration, supporting a causal role for this program in disease progression. We further show that GPNMB+ macrophages promote osteogenic differentiation and degeneration of NP cells through PDGF signaling and that inhibition of PDGF signaling reduces NP cell osteogenic reprogramming and alleviates disc degeneration. Together, these findings define immune-driven osteogenic reprogramming of NP cells as a key pathological mechanism in IVDD and highlight NP cell osteogenic differentiation as a potential therapeutic target.

Keywords
cell-cell communication; intervertebral disc degeneration; macrophages; nucleus pulposus; osteogenic differentiation; single-cell RNA sequencing.
Products