Journal
MECHANISMS OF AGEING AND DEVELOPMENT
Volume 207, Issue -, Pages -Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mad.2022.111715
Keywords
Senescence; Angiogenesis; Intervertebral disc degeneration; Klotho; Extracellular matrix
Categories
Funding
- Aging and Health of Women and Children Research Project of Shanghai Municipal Health Commission, China
- Training Program for Academic and Tech-nical Leaders of Major Disciplines in Jiangxi Province-Leading Talents Project, China
- Ji?an Science and Technology Planning Project, China
- Key Projects of Natural Science Foundation of Jiangxi Province, China
- [2020YJZX0116]
- [20213BCJ22011]
- [20211-025299]
- [20212ACB206032]
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The study reveals that the anti-aging drug Klotho can inhibit the progression of intervertebral disc degeneration by improving extracellular matrix degradation and angiogenesis to maintain the phenotype, viability, and matrix content of nucleus pulposus cells (NPCs).
Intervertebral disc degeneration (IDD) is highly ubiquitous in the aged population and is an essential factor for low back pain and spinal disability. Because of the association between IDD and senescence, we investigated the ability of the anti-aging drug Klotho to inhibit age-dependent advancement of nucleus pulposus cell (NPC) degeneration. The results indicated that 400 pM exogenous Klotho significantly ameliorated extracellular matrix degradation and angiogenesis. Moreover, we demonstrated that the suppression of angiogenesis and extracellular matrix catabolism was related to inhibition of the Ras-related C3 botulinum toxin substrate 1 (Rac1)/PAK1 axis and matrix metalloproteinase 2 protein expression by exogenous Klotho cotreatment with a Rac1 inhibitor, gene overexpression in NPCs, and stimulation of human umbilical vein endothelial cells with conditioned medium from NPCs. The treatment also preserved the NPC phenotype, viability, and matrix content. In conclusion, these results suggest that the new anti-aging drug Klotho is a potential treatment strategy to mitigate IDD, and thus, provides an innovative understanding of the molecular mechanism of IDD.Data availability: All data supporting the findings of this study are available from the corresponding authors upon reasonable request.
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