Nucleus Pulposus Cell Senescence in IVDD: Mechanisms and Therapeutic Perspectives

Feng Jiang

doi:10.54097/2ggt8s93

Authors

Feng Jiang

DOI:

https://doi.org/10.54097/2ggt8s93

Keywords:

Intervertebral Disc Degeneration, Senescence, Mechanism, Nucleus Pulposus Cells

Abstract

Intervertebral disc degeneration (IVDD) is a common spinal pathological process that leads to the degeneration of the structure and function of the intervertebral disc, causing low back pain and nerve root compression. The molecular mechanism of intervertebral disc degeneration is not fully understood, but cellular senescence is an important factor. This article summarizes the characteristics, causes, signal transduction pathways and treatment methods of cellular senescence in intervertebral disc degeneration, including inhibiting the expression or activity of genes or signal pathways related to cellular senescence, increasing the number or function of intervertebral disc cells, and improving the microenvironment of the intervertebral disc. This article aims to provide new clues for the prevention and treatment of intervertebral disc degeneration.

Downloads

Download data is not yet available.

References

[1] Wang F, Cai F, Shi R, et al. Aging and age related stresses: a senescence mechanism of intervertebral disc degeneration[J]. Osteoarthritis and Cartilage, 2016, 24(3): 398–408.

[2] Feng C, Liu H, Yang M, et al. Disc cell senescence in intervertebral disc degeneration: causes and molecular pathways[J]. Cell Cycle, 2016, 15(13): 1674–1684.

[3] Patil P, Niedernhofer L J, Robbins P D, et al. Cellular senescence in intervertebral disc aging and degeneration[J]. Current Molecular Biology Reports, 2018, 4(4): 180–190.

[4] Wu Y, Shen S, Shi Y, et al. Senolytics: eliminating senescent cells and alleviating intervertebral disc degeneration[J/OL]. Frontiers in Bioengineering and Biotechnology, 2022, 10.

[5] Wang F, Wang Y, Wu X. Advances of nucleus pulposus cells for treating intervertebral disc degeneration[J]. Chinese Journal of Reparative and Reconstructive Surgery, 2009, 23(7): 864–867.

[6] Molladavoodi S, McMorran J, Gregory D. Mechanobiology of annulus fibrosus and nucleus pulposus cells in intervertebral discs[J]. Cell and Tissue Research, 2020, 379(3): 429–444.

[7] Childs B G, Gluscevic M, Baker D J, et al. Senescent cells: an emerging target for diseases of ageing[J]. Nature Reviews. Drug Discovery, 2017, 16(10): 718–735.

[8] Wang D, Shang Q, Mao J, et al. Phosphorylation of krt8 (keratin 8) by excessive mechanical load-activated pkn (protein kinase n) impairs autophagosome initiation and contributes to disc degeneration[J]. Autophagy, 2023: 1–19.

[9] Wu J, Chen Y, Liao Z, et al. Self-amplifying loop of nf-κb and periostin initiated by piezo1 accelerates mechano-induced senescence of nucleus pulposus cells and intervertebral disc degeneration[J]. Molecular Therapy: The Journal of the American Society of Gene Therapy, 2022, 30(10): 3241–3256.

[10] Liu C, Liu L, Yang M, et al. A positive feedback loop between ezh2 and nox4 regulates nucleus pulposus cell senescence in age-related intervertebral disc degeneration[J]. Cell Division, 2020, 15: 2.

[11] Sharpless N E, Sherr C J. Forging a signature of in vivo senescence[J]. Nature Reviews. Cancer, 2015, 15(7): 397–408.

[12] Cai Y, Song W, Li J, et al. The landscape of aging[J]. Science China. Life Sciences, 2022, 65(12): 2354–2454.

[13] Yang H, Yang X, Rong K, et al. Eupatilin attenuates the senescence of nucleus pulposus cells and mitigates intervertebral disc degeneration via inhibition of the mapk/nf-κb signaling pathway[J]. Frontiers in Pharmacology, 2022, 13: 940475.

[14] Ngo K, Patil P, McGowan S J, et al. Senescent intervertebral disc cells exhibit perturbed matrix homeostasis phenotype[J]. Mechanisms of Ageing and Development, 2017, 166: 16–23.

[15] Pan Y, Gu Z, Lyu Y, et al. Link between senescence and cell fate: senescence-associated secretory phenotype and its effects on stem cell fate transition[J]. Rejuvenation Research, 2022, 25(4): 160–172.

[16] Li S, Pan X, Wu Y, et al. IL-37 alleviates intervertebral disc degeneration via the il-1r8/nf-κb pathway[J]. Osteoarthritis and Cartilage, 2023, 31(5): 588–599.

[17] Aman Y, Schmauck-Medina T, Hansen M, et al. Autophagy in healthy aging and disease[J]. Nature Aging, 2021, 1(8): 634–650.

[18] Rajendran P, Alzahrani A M, Hanieh H N, et al. Autophagy and senescence: a new insight in selected human diseases[J]. Journal of Cellular Physiology, 2019, 234(12): 21485–21492.

[19] Kang C, Elledge S J. How autophagy both activates and inhibits cellular senescence[J]. Autophagy, 2016, 12(5): 898–899.

[20] Vicencio, José M, Galluzzi, et al. Senescence, apoptosis or autophagy[J]. Gerontology, 2008, 54(2): 92–99.

[21] Leidal A M, Levine B, Debnath J. Autophagy and the cell biology of age-related disease[J]. Nature Cell Biology, 2018, 20(12): 1338–1348.

[22] Xu C, Wang L, Fozouni P, et al. SIRT1 is downregulated by autophagy in senescence and ageing[J]. Nature Cell Biology, 2020, 22(10): 1170–1179.

[23] Rey-Millet M, Pousse M, Soithong C, et al. Senescence-associated transcriptional derepression in subtelomeres is determined in a chromosome-end-specific manner[J]. Aging Cell, 2023, 22(5): e13804.

[24] Han Y, Zhou C-M, Shen H, et al. Attenuation of ataxia telangiectasia mutated signalling mitigates age-associated intervertebral disc degeneration[J]. Aging Cell, 2020, 19(7): e13162.

[25] Huang X, Ni B, Xi Y, et al. Protease-activated receptor 2 (par-2) antagonist az3451 as a novel therapeutic agent for osteoarthritis[J]. Aging, 2019, 11(24): 12532–12545.

[26] Li S, Pan X, Wu Y, et al. IL-37 alleviates intervertebral disc degeneration via the il-1r8/nf-κb pathway[J]. Osteoarthritis and Cartilage, 2023, 31(5): 588–599.

[27] Suda M, Shimizu I, Katsuumi G, et al. Glycoprotein nonmetastatic melanoma protein b regulates lysosomal integrity and lifespan of senescent cells[J]. Scientific Reports, 2022, 12(1): 6522.

[28] Birch J, Gil J. Senescence and the sasp: many therapeutic avenues[J]. Genes & Development, 2020, 34(23–24): 1565–1576.

[29] Gasek N S, Kuchel G A, Kirkland J L, et al. Strategies for targeting senescent cells in human disease[J]. Nature Aging, 2021, 1(10): 870–879.

[30] Kirkland J L, Tchkonia T. Cellular senescence: a translational perspective[J]. EBioMedicine, 2017, 21: 21–28.

[31] Ogrodnik M, Zhu Y, Langhi L G P, et al. Obesity-induced cellular senescence drives anxiety and impairs neurogenesis[J]. Cell Metabolism, 2019, 29(5): 1061-1077.e8.

[32] Song X, Dai J, Li H, et al. Anti-aging effects exerted by tetramethylpyrazine enhances self-renewal and neuronal differentiation of rat bmscs by suppressing nf-kb signaling[J]. Bioscience Reports, 2019, 39(6): BSR20190761.

[33] Suda M, Shimizu I, Katsuumi G, et al. Senolytic vaccination improves normal and pathological age-related phenotypes and increases lifespan in progeroid mice[J]. Nature Aging, 2021, 1(12): 1117–1126.

[34] [34] Sun Y, Li Q, Kirkland J L. Targeting senescent cells for a healthier longevity: the roadmap for an era of global aging[J]. Life Medicine, 2022, 1(2): 103–119.

[35] Song S, Lam E W-F, Tchkonia T, et al. Senescent cells: emerging targets for human aging and age-related diseases[J]. Trends in Biochemical Sciences, 2020, 45(7): 578–592.

[36] Chang J, Wang Y, Shao L, et al. Clearance of senescent cells by abt263 rejuvenates aged hematopoietic stem cells in mice[J]. Nature Medicine, 2016, 22(1): 78–83.

[37] Kirkland J L, Tchkonia T. Senolytic drugs: from discovery to translation[J]. Journal of Internal Medicine, 2020, 288(5): 518–536.

[38] Zhu Y, Doornebal E J, Pirtskhalava T, et al. New agents that target senescent cells: the flavone, fisetin, and the bcl-xl inhibitors, a1331852 and a1155463[J]. Aging, 2017, 9(3): 955–963.

[39] Zhang L, Pitcher L E, Prahalad V, et al. Targeting cellular senescence with senotherapeutics: senolytics and senomorphics[J]. The FEBS Journal, 2023, 290(5): 1362–1383.

[40] Kirkland J L, Tchkonia T, Zhu Y, et al. The clinical potential of senolytic drugs[J]. Journal of the American Geriatrics Society, 2017, 65(10): 2297–2301.

[41] Yoon D S, Choi Y, Jang Y, et al. SIRT1 directly regulates sox2 to maintain self-renewal and multipotency in bone marrow-derived mesenchymal stem cells[J]. Stem Cells (Dayton, Ohio), 2014, 32(12): 3219–3231.

[42] Xia W, Hou M. Macrophage migration inhibitory factor rescues mesenchymal stem cells from doxorubicin-induced senescence though the pi3k-akt signaling pathway[J]. International Journal of Molecular Medicine, 2018, 41(2): 1127–1137.

[43] Molladavoodi S, McMorran J, Gregory D. Mechanobiology of annulus fibrosus and nucleus pulposus cells in intervertebral discs[J]. Cell and Tissue Research, 2020, 379(3): 429–444.

[44] Chen J, Zhu H, Zhu Y, et al. Injectable self-healing hydrogel with sirna delivery property for sustained sting silencing and enhanced therapy of intervertebral disc degeneration[J]. Bioactive Materials, 2022, 9: 29–43.

[45] Sharma M, Hunter K D, Fonseca F P, et al. Emerging role of cellular senescence in the pathogenesis of oral submucous fibrosis and its malignant transformation[J]. Head & Neck, 2021, 43(10): 3153–3164.

[46] Mbara K C, Devnarain N, Owira P M O. Potential role of polyphenolic flavonoids as senotherapeutic agents in degenerative diseases and geroprotection[J]. Pharmaceutical Medicine, 2022, 36(6): 331–352.

[47] Kirkland J L, Tchkonia T. Cellular senescence: a translational perspective[J]. EBioMedicine, 2017, 21: 21–28.