Progerin accumulation in nucleus pulposus cells impairs mitochondrial function and induces intervertebral disc degeneration and therapeutic effects of sulforaphane
Xu X, Wang D, Zheng C, Gao B, Fan J, Cheng P, Liu B, Yang L, Luo Z
Theranostics · 92 citations
How it was studied
- Design
- In vitro/mechanistic study (classified by our AI screen)
- Studied in
- People, plus animal or lab work
- Main outcome
- Health markers and function
Who paid for it
- Funding
- Independent funding
- Government
- National Natural Science Foundation of China
- Grants
- National Natural Science Foundation of China (81772377); National Natural Science Foundation of China (81730065); National Natural Science Foundation of China (81572192)
Based on 1 listed funder(s).
Publication
- Published
- 2019-01-01 · Theranostics · vol. 9 · issue 8 · pp. 2252–2267
- Publisher
- Ivyspring International Publisher
- Cited
- 120 citations · more than 94% of similar papers · 3.5× the field average
- Impact
- Top 10% most cited in its field
- References
- 76 works
- Access
- Open access (journal) · CC-BY-NC
- Research areas
- Nuclear Structure and Function · Skin and Cellular Biology Research · Retinoids in leukemia and cellular processes
- Keywords
- LMNA, Lamin, Cell biology, Apoptosis, TUNEL assay, Mitochondrion, Biology, Chemistry, Nucleus, Biochemistry
- MeSH
- cell line, mitochondria, animals, humans, mice, rats, isothiocyanates, sulfoxides, collagen, lamin type a, adenosine triphosphate, anticarcinogenic agents, apoptosis, adolescent, adult, female, male, aggrecans, matrix metalloproteinase 13, intervertebral disc degeneration, mitochondrial dynamics, nucleus pulposus
9 authors
From CN
- Xiaolong XuXijing Hospital; Air Force Medical University
- Di WangXijing Hospital; Air Force Medical University
- Chao ZhengXijing Hospital; Air Force Medical University
- Bo GaoXijing Hospital; Air Force Medical University
- Jing FanXijing Hospital; Air Force Medical University
- Pengzhen ChengXijing Hospital; Air Force Medical University
Abstract
Progerin, a truncated unprocessed lamin A protein, causes tissue aging and degeneration. In this study we explored the role of progerin in the pathogenesis of intervertebral disc degeneration (IDD). We also examined the effect of sulforaphane (SFN) on progerin accumulation and mitochondrial dysfunction in IDD. Methods: The role of progerin in IDD was explored using human nucleus pulposus (NP) tissues, rat NP cells, and Lmna G609G knock-in mice. Immunostaining, X-ray imaging, and Western blotting were performed to assess the phenotypes of intervertebral discs. Alterations in senescence and apoptosis were evaluated by SA-β-galactosidase, immunofluorescence, flow cytometry, and TUNEL assays. Mitochondrial function was investigated by JC-1 staining, transmission electron microscopy, and determination of the level of ATP and the activities of mitochondrial enzymes. Results: The progerin level was elevated in degenerated human NP tissues. Lmna G609G/G609G mice displayed IDD, as evidenced by increased matrix metalloproteinase-13 expression and decreased collagen II and aggrecan expression and disc height. Furthermore, progerin overexpression in rat NP cells induced mitochondrial dysfunction (decreased ATP synthesis, mitochondrial membrane potential, and activities of mitochondrial complex enzymes), morphologic abnormalities, and disrupted mitochondrial dynamic (abnormal expression of proteins involved in fission and fusion), resulting in apoptosis and senescence. SFN ameliorated the progerin-induced aging defects and mitochondrial dysfunction in NP cells and IDD in Lmna G609G/G609G mice. Conclusions: Progerin is involved in the pathogenesis of IDD. Also, SFN alleviates progerin‑induced IDD, which is associated with amelioration of aging defects and mitochondrial dysfunction. Thus, SFN shows promise for the treatment of IDD.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY-NC).
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