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KMID : 1034820230190020255
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Molecular & Cellular Toxicology
2023 Volume.19 No. 2 p.255 ~ p.264
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Amphiregulin secreted by cartilage endplate stem cells inhibits intervertebral disk degeneration and TNF-α production via PI3K/AKT and ERK1/2 signaling pathways
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Qin Chen
Yaohong Wu
Mingliang Zhong
Chanhua Xu
Rongchun Chen
Ning Liu
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Abstract
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Background : Intervertebral disk degeneration (IDD) is a common orthopedic disorder, and nucleus pulposus cells (NPCs) serve to stabilize the intervertebral disk.
Objective : This study was implemented to explore the protective effect of endplate stem cells (EPSCs) on IDD. NPCs and EPSCs were isolated from rats and tert-Butyl peroxide (TBHP) was used to treat NPCs and simulate IDD. EPSC-derived conditioned medium (CM) was collected and mixed with a culture medium at different proportions, which was then used to treat NPCs. SOD assay was employed to examine the oxidative stress level in the NPCs. To assess apoptosis and caspase-3 activity, flow cytometry and western blots for cleaved PARP1 and BAX were carried out. The mRNA expression levels of different genes were detected by quantitative real-time polymerase chain reaction. Furthermore, the concentrations of amphiregulin (Areg) and inflammatory factors were measured with ELISA kits and cell signaling pathways were evaluated using western blotting.
Results : Following TBHP treatment, caspase-3 activity in the NPCs increased. However, exposing TBHP-induced NPCs to the EPSC-derived CM reduced oxidative stress, caspase-3 activity, cell apoptosis, fibrotic response, and cytokine production. Additionally, the EPSC-derived CM contained a higher concentration of Areg compared to that in the NPCs. Furthermore, Areg decreased oxidative stress, cell apoptosis, fibrosis, and inflammation via both PI3K/AKT and ERK1/2 signaling pathways.
Conclusion : ECSCs reduce NPC apoptosis, oxidative stress, production of inflammatory factors, and fibrotic response via the release of Areg. Moreover, Areg can exert these protective effects on NPCs via PI3K/AKT and ERK1/2 signaling pathways.
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KEYWORD
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Intervertebral disk degeneration, Endplate stem cells, Amphiregulin, Nucleus pulposus cells
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