Mesenchymal stem cells regulate inflammatory milieu within degenerative nucleus pulposus cells via p38&nbsp;MAPK pathway

Zhao,Yuanting; Qin,Yue; Wu,Shufang; Huang,Dageng; Hu,Huimin; Zhang,Xinliang; Hao,Dingjun

doi:10.3892/etm.2020.9150

Mesenchymal stem cells regulate inflammatory milieu within degenerative nucleus pulposus cells via p38 MAPK pathway

Authors:
- Yuanting Zhao
- Yue Qin
- Shufang Wu
- Dageng Huang
- Huimin Hu
- Xinliang Zhang
- Dingjun Hao
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Affiliations: Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, P.R. China, Department of Anesthesiology, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, P.R. China, Center for Translational Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
Published online on: August 27, 2020 https://doi.org/10.3892/etm.2020.9150
Article Number: 22

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Abstract

It has been established that excessive apoptosis of nucleus pulposus cells (NPCs) are responsible for pathogenesis of human intervertebral disc degeneration (IDD). The present study aimed to shed light on the molecular mechanisms underlying the protective effects of mesenchymal stem cells (MSCs) on NPCs in an inflammatory environment. NPCs were treated with TNF‑α to induce inflammation and then co‑cultured with Wharton's Jelly‑derived MSCs (WJ‑MSCs)without direct interaction. The levels of inflammation markers (IL‑1β, IL‑6 and IL‑8) in NPCs were detected by performing enzyme‑linked immunosorbent assay (ELISA), and expression of metalloproteases and aggrecan, as well as the activity of p38 MAPK pathway were determined through immunoblotting. SB‑203580 was used to inhibit p38 signaling, prior to evaluation of the effects of Wharton's Jelly‑derived MSCs (WJ‑MSCs) on inflammatory response within the co‑cultured NPCs. After TNF‑α treatment, the levels of inflammatory cytokines, MMP‑3, and MMP‑13 in NPCs were increased whereas aggrecan was decreased, which was then dramatically reversed by WJ‑MSCs co‑culture. Likewise, WJ‑MSCs suppressed TNF‑α‑induced phosphorylation of p38 MAPK signaling components including p38, ASK‑1, MKK‑3 and MKK‑6. Blocking p38 MAPK pathway enhanced the anti‑inflammatory impact of WJ‑MSCs, and there was no significant difference between NPCs co‑cultured with WJ‑MSCs or the cells cultured alone. WJ‑MSCs co‑culture mitigate TNF‑α‑induced inflammatory response and ECM degeneration in NPCs, the major pathological events are implicated in IDD development, probably by suppressing the p38 MAPK signaling cascade.

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