bioRxivCell Biology
Senolytic Treatment for Low Back Pain.
M. Mannarino, H. Cherif, S. Ghazizadeh, O. W. Martinez, K. Sheng, E. Cousineau, S. Lee, L. S. Stone, M. Millecamps, C. Gao, J. A. Ouellet, L. Haglund
Abstract
Senescent cells (SnCs) accumulate due to aging and external cellular stress throughout the body. They adopt a senescence-associated secretory phenotype (SASP) and release inflammatory, and degenerative factors that actively contribute to age-related diseases such as low back pain (LBP). The senolytics, o-Vanillin and RG-7112, remove senescent human intervertebral (IVD) cells and reduce SASP release, but it is not known if they can treat LBP. sparc-/- mice, with LBP, were treated orally with o-Vanillin and RG-7112 as single or combination treatments. Treatment reduced LBP and SASP factor release and removed SnCs from the IVD and spinal cord. Treatment also lowered degeneration score in the IVDs, improved vertebral bone quality, and reduced the expression of pain markers in the spinal cord. The result indicates that RG-7112 and o-Vanillin with the combination treatment providing the strongest effect are potential disease-modifying drugs for LBP and other painful disorders where cell senescence is implicated. One Sentence Summary: Senolytics drugs can reduce back pain
- organism: mouse
- research focus: host-pathogen & immune response
- research focus: differential expression
- research focus: cell type annotation
- approach: experimental assay
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