Elimination of Senescent Cells by Senolytics Facilitates Bony Endplate Microvessel Formation and Mitigates Disc Degeneration in Aged Mice

作者：Bolin Chen, Runjiu Zhu, Hao Hu, Mingbin Zhan, Tingxuan Wang, Fangli Huang, Fuxin Wei, Yu Chai, Zemin Ling, Xuenong Zou · 发表于：Frontiers in Cell and Developmental Biology · 年份：2022 · DOI：10.3389/fcell.2022.853688 · 被引用次数：23 · 研究领域：Spine and Intervertebral Disc Pathology、Musculoskeletal pain and rehabilitation、Pregnancy-related medical research

Senolytics are a class of drugs that selectively eliminate senescent cells and ameliorate senescence-associated disease. Studies have demonstrated the accumulation of senescent disc cells and the production of senescence-associated secretory phenotype decrease the number of functional cells in degenerative tissue. It has been determined that clearance of senescent cell by senolytics rejuvenates various cell types in several human organs, including the largest avascular structure, intervertebral disc (IVD). The microvasculature in the marrow space of bony endplate (BEP) are the structural foundation of nutrient exchange in the IVD, but to date, the anti-senescence effects of senolytics on senescent vascular endothelial cells in the endplate subchondral vasculature remains unclear. In this study, the relationships between endothelial cellular senescence in the marrow space of the BEP and IVD degeneration were investigated using the aged mice model. Immunofluorescence staining was used to evaluate the protein expression of P16, P21, and EMCN in vascular endothelial cells. Senescence-associated β-galactosidase staining was used to investigate the senescence of vascular endothelial cells. Meanwhile, the effects of senolytics on cellular senescence of human umbilical vein endothelial cells were investigated using a cell culture model. Preliminary results showed that senolytics alleviate endothelial cellular senescence in the marrow space of BEP as evidenced by reduced senescence-as...