Platelet-Derived Growth Factor-BB Inhibits Intervertebral Disc Degeneration via Suppressing Pyroptosis and Activating the MAPK Signaling Pathway

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.

Mesenchymal Stem Cells May Alleviate the Intervertebral Disc Degeneration by Reducing the Oxidative Stress in Nucleus Pulposus Cells

“…The most enriched biological process was Response to oxidative stress, cellular component was Cytoplasm, and molecular function was Identical protein binding. More importantly, we also investigated the potential signaling pathways involved in the repair process of NPCs cocultured with MSCs, and some of these signaling pathways have been proved to play important roles in the pathophysiology of IDD [38][39][40][41][42]. TNF signaling pathway and IL-17 signaling pathway both were inflammation-related pathways, which indicated that MSCs might reduce the oxidative stress, and then improve the inflammatory status of degenerative NPCs [38,39].…”

“…TNF signaling pathway and IL-17 signaling pathway both were inflammation-related pathways, which indicated that MSCs might reduce the oxidative stress, and then improve the inflammatory status of degenerative NPCs [38,39]. MAPK signaling pathway was another vital biolog-ical pathway in the development of IDD [40][41][42] 7 Stem Cells International degenerative NPCs cocultured with MSCs. Both relaxin and oxytocin have been demonstrated to exert important protective effects in human diseases by inhibiting the cell apoptosis [43][44][45][46][47].…”

“…TNF signaling pathway and IL-17 signaling pathway both were inflammation-related pathways, which indicated that MSCs might reduce the oxidative stress, and then improve the inflammatory status of degenerative NPCs [ 38 , 39 ]. MAPK signaling pathway was another vital biological pathway in the development of IDD [ 40 – 42 ]. Zhang et al reported that platelet-derived growth factor-BB could prevent the IDD through activating the MAPK signaling pathway [ 40 ].…”

“…MAPK signaling pathway was another vital biological pathway in the development of IDD [ 40 – 42 ]. Zhang et al reported that platelet-derived growth factor-BB could prevent the IDD through activating the MAPK signaling pathway [ 40 ]. Cui et al study showed that microRNA-129-5p could alleviate the IDD via blocking the LRG1-mediated p38 MAPK activation [ 41 ].…”

Targeting Autophagy for Developing New Therapeutic Strategy in Intervertebral Disc Degeneration

“…Therefore, some growth factors are considered as a possible therapeutic to improve IVD tissue regeneration. Indeed, platelet-derived growth factor (PDGF), insulin-like growth factor 1 (IGF-1), growth differentiation factor 5 (GDF-5), bone morphogenetic protein 2 (BMP-2), and bone morphogenetic protein 7 (BMP-7) have been explored as viable treatment alternatives for IVD regeneration [ 151 , 152 , 153 , 154 , 155 , 156 , 157 , 158 , 159 , 160 , 161 , 162 , 163 ]. Furthermore, VEGF is highly expressed in the injured IVD, and mutational variations in the VEGF gene are associated with lumbar disc degeneration in a young Korean population [ 164 ].…”