Senescence of endplate osteoclasts induces sensory innervation and spinal pain

Dayu Pan, Kheiria Gamal Benkato, Xuequan Han, Jinjian Zheng, Vijay Kumar, Mei Wan, Junying Zheng, Xu Cao

Research output: Contribution to journalArticlepeer-review

Abstract

Spinal pain affects individuals of all ages and is the most common musculoskeletal problem globally. Its clinical management remains a challenge as the underlying mechanisms leading to it are still unclear. Here, we report that significantly increased numbers of senescent osteoclasts (SnOCs) are observed in mouse models of spinal hypersensitivity, like lumbar spine instability (LSI) or aging, compared to controls. The larger population of SnOCs is associated with induced sensory nerve innervation, as well as the growth of H-type vessels, in the porous endplate. We show that deletion of senescent cells by administration of the senolytic drug Navitoclax (ABT263) results in significantly less spinal hypersensitivity, spinal degeneration, porosity of the endplate, sensory nerve innervation, and H-type vessel growth in the endplate. We also show that there is significantly increased SnOC-mediated secretion of Netrin-1 and NGF, two well-established sensory nerve growth factors, compared to non-senescent OCs. These findings suggest that pharmacological elimination of SnOCs may be a potent therapy to treat spinal pain.

Original languageEnglish (US)
JournaleLife
Volume12
DOIs
StatePublished - Jun 19 2024

Keywords

  • H-type vessle
  • endplate
  • low back pain
  • medicine
  • mouse
  • osteoclast
  • senescence
  • sensory nerve

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology

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