Abstract
Platelet-derived growth factor-BB (PDGF-BB) is a cytokine involved in tissue repair and tumor progression. It has been found to have expression differences between normal and degenerative intervertebral discs. However, it is not clear whether PDGF-BB has a protective effect on intervertebral disc degeneration (IDD). In this experiment, we treated nucleus pulposus cells (NPCs) with IL-1β to simulate an inflammatory environment and found that the extracellular matrix (ECM) anabolic function of NPCs in an inflammatory state was inhibited. Moreover, the induction of IL-1β also enhanced the expression of NLRP3 and the cleavage of caspase-1 and IL-1β, which activated the pyroptosis of NPCs. In this study, we studied the effect of PDGF-BB on IL-1β-treated NPCs and found that PDGF-BB not only significantly promotes the ECM anabolism of NPCs, but also inhibits the occurrence of pyroptosis and the production of pyroptosis products of NPCs. Consistent with this, when we used imatinib to block the PDGF-BB receptor, the above-mentioned protective effect disappeared. In addition, we found that PDGF-BB can also promote the ECM anabolism of NPCs by regulating the ERK, JNK, PI3K/AKT signaling pathways, but not the P38 signaling pathway. In vivo studies, mice that blocked PDGF-BB receptors showed more severe histological manifestations of intervertebral disc degeneration. In summary, our results indicate that PDGF-BB participates in inhibiting the occurrence and development of IDD by inhibiting pyroptosis and regulating the MAPK signaling pathway.
Highlights
Intervertebral disc degeneration (IDD) is recognized as the main cause of low back pain (Wuertz and Haglund, 2013; Risbud and Shapiro, 2014; Yelin et al, 2016; Kos et al, 2019)
Platelet-derived growth factor-BB (PDGF-BB), as a growth factor that can stimulate the growth of connective tissue and other tissue cells, has been extensively studied in tumor and angiogenesis
Since Tolonen et al (1997) first discovered that PDGF-BB is expressed in intervertebral disc, the role of PDGF-BB in the mechanism of intervertebral disc degeneration has received attention (Gruber et al, 2000; Paglia et al, 2016)
Summary
Intervertebral disc degeneration (IDD) is recognized as the main cause of low back pain (Wuertz and Haglund, 2013; Risbud and Shapiro, 2014; Yelin et al, 2016; Kos et al, 2019). The anabolism and catabolism of the extracellular matrix (ECM) of the intervertebral disc (IVD) are kept in balance (Cui and Zhang, 2020; Chen et al, 2021). When the intervertebral disc is in an inflammatory environment or infection, it is often accompanied by a decrease in ECM anabolism and an increase in catabolism (Wang et al, 2016; Li et al, 2017; Tang et al, 2021). This imbalance will lead to changes in the water content, height reduction, and abnormal stress distribution in the intervertebral disc, thereby accelerating the degeneration of the intervertebral disc (Lan et al, 2021).
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