期刊
AGING CELL
卷 21, 期 4, 页码 -出版社
WILEY
DOI: 10.1111/acel.13577
关键词
cellular senescence; intervertebral disc degeneration; nucleus pulposus cells; reprogramming
资金
- National Natural Science Foundation of China [82002327, 82072481]
The findings of this study suggest that partial reprogramming through short-term induction of OSKM can inhibit IDD progression and reduce senescence in aging NPCs. Mechanistically, this partial reprogramming activates energy metabolism and promotes redistribution of the cytoskeleton to restore the aging state of NPCs.
Rejuvenation of nucleus pulposus cells (NPCs) in degenerative discs can reverse intervertebral disc degeneration (IDD). Partial reprogramming is used to rejuvenate aging cells and ameliorate progression of aging tissue to avoiding formation of tumors by classical reprogramming. Understanding the effects and potential mechanisms of partial reprogramming in degenerative discs provides insights for development of new therapies for IDD treatment. The findings of the present study show that partial reprogramming through short-term cyclic expression of Oct-3/4, Sox2, Klf4, and c-Myc (OSKM) inhibits progression of IDD, and significantly reduces senescence related phenotypes in aging NPCs. Mechanistically, short-term induction of OSKM in aging NPCs activates energy metabolism as a energy switch by upregulating expression of Hexokinase 2 (HK2) ultimately promoting redistribution of cytoskeleton and restoring the aging state in aging NPCs. These findings indicate that partial reprogramming through short-term induction of OSKM has high therapeutic potential in the treatment of IDD.
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