The effect of prolonged rhBMP-2 treatment on telomerase activity, replicative capacity and senescence of human nucleus pulposus cells

Kim, Ki-Won; Jeong, Seo-Won; Park, Hyung-Youl; Heu, Jun-Young; Jung, Ho-Young; Lee, Jung Hoon

doi:10.1080/10520295.2020.1721560

Cited by 2 publications

(1 citation statement)

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“…Osteogenic protein-1 (OP-1), also known as BMP-7, can inhibit subculture- or TNF-α-induced senescence in NP cells [ 53 , 124 ]. In contrast, prolonged treatment of NP cells with a high dose of recombinant human BMP-2 (rhBMP-2) is reported to increase SA-β-gal activity and p53, p21, and p16 INK4a expression, [ 177 ] suggesting the adverse effects of long-term exposure to growth factors. Omentin-1, one of the adipokines derived from white adipose tissue, attenuated IL-1β-induced CS through activation of SIRT1 [ 169 ].…”

Section: Therapeuticsmentioning

confidence: 99%

Cellular Senescence in Intervertebral Disc Aging and Degeneration: Molecular Mechanisms and Potential Therapeutic Opportunities

et al. 2023

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Closely associated with aging and age-related disorders, cellular senescence (CS) is the inability of cells to proliferate due to accumulated unrepaired cellular damage and irreversible cell cycle arrest. Senescent cells are characterized by their senescence-associated secretory phenotype that overproduces inflammatory and catabolic factors that hamper normal tissue homeostasis. Chronic accumulation of senescent cells is thought to be associated with intervertebral disc degeneration (IDD) in an aging population. This IDD is one of the largest age-dependent chronic disorders, often associated with neurological dysfunctions such as, low back pain, radiculopathy, and myelopathy. Senescent cells (SnCs) increase in number in the aged, degenerated discs, and have a causative role in driving age-related IDD. This review summarizes current evidence supporting the role of CS on onset and progression of age-related IDD. The discussion includes molecular pathways involved in CS such as p53-p21CIP1, p16INK4a, NF-κB, and MAPK, and the potential therapeutic value of targeting these pathways. We propose several mechanisms of CS in IDD including mechanical stress, oxidative stress, genotoxic stress, nutritional deprivation, and inflammatory stress. There are still large knowledge gaps in disc CS research, an understanding of which will provide opportunities to develop therapeutic interventions to treat age-related IDD.

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