Senescent cells generate inflammatory signaling that is disruptive to tissue structure and function when sustained for the long term. The lingering presence of senescent cells is considered a driving mechanism for many inflammatory conditions, including intervertebral disc degeneration. Here, researchers demonstrate in cell models that recombinant PDGF can be used to suppress the markers of the presence of cellular senescence, though it remains to be seen as to whether it achieves this outcome by destroying senescent cells, reprogramming them, or preventing their creation.
Low back pain (LBP), ranked as the first cause of years lived with disability, is a prevalent condition. Although the etiology of LBP is multifactorial, a major contributor of LBP is intervertebral disc (IVD) degeneration. The IVD consists of three compartments: the gelatinous nucleus pulposus (NP), fibrous annulus fibrosus (AF), and cartilaginous endplate.
Cellular senescence, triggered by normal cells in response to various intrinsic and extrinsic stressors, is a fundamental mechanism underlying age-related chronic diseases. Senescent cells are featured by irreversible growth arrest and acquire a senescent-associated secretory phenotype (SASP) and the secretion of pro-inflammatory cytokines, chemokines, and tissue-damaging proteases. In the IVD, it has been well established that the number of senescent cells increases with aging and IVD degeneration.
Previous studies have highlighted that platelet-derived growth factor (PDGF) mitigated IVD degeneration through anti-apoptosis, anti-inflammation, and pro-anabolism. However, its impact on IVD cell senescence remains elusive. PDGF is a major constituent of platelet rich plasma (PRP), which is widely used in the clinical setting for tissue regeneration and repair. It can be made of a homodimer of A, B, C, and D polypeptide chains, or an AB heterodimer. Among these, PDGF-AB and -BB are the predominant forms in PRPs. In this study, human NP and AF cells derived from aged, degenerated IVDs were treated with recombinant human (rh) PDGF-AB/BB for 5 days and changes of transcriptome profiling were examined through mRNA sequencing.
PDGF-AB/BB treatment resulted in downregulation of gene clusters related to neurogenesis and response to mechanical stimulus in AF cells while the downregulated genes in NP cells were mainly associated with metabolic pathways. In both NP and AF cells, PDGF-AB and BB treatment upregulated the expression of genes involved in cell cycle regulation, mesenchymal cell differentiation, and response to reduced oxygen levels, while downregulating the expression of genes related to the SASP, including oxidative stress, reactive oxygen species (ROS), and mitochondrial dysfunction. The rhPDGF-AB/BB treatment mitigated the senescence progression through increased cell population in the S phase, reduced SA-β-Gal activity, and decreased expression of senescence related regulators including P21, P16, IL6, and NF-κB. Our findings reveal a novel anti-senescence role of PDGF in the IVD, making it a promising potential candidate to delay aging-induced IVD degeneration.
Link: https://doi.org/10.7554/eLife.103073.2
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