S1PR3 suppresses the inflammatory response and extracellular matrix degradation in human nucleus pulposus cells

Tian,Zhen; Gao,Haoran; Xia,Wenjun; Lou,Zhaohui

doi:10.3892/etm.2024.12553

S1PR3 suppresses the inflammatory response and extracellular matrix degradation in human nucleus pulposus cells

Authors:
- Zhen Tian
- Haoran Gao
- Wenjun Xia
- Zhaohui Lou
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Affiliations: Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
Published online on: April 25, 2024 https://doi.org/10.3892/etm.2024.12553
Article Number: 265
Copyright: © Tian et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Sphingosine 1‑phosphate receptor 3 (S1PR3) participates in the inflammatory response in multiple types of diseases. However, the biological role of S1PR3 in intervertebral disc degeneration and the underlying mechanism are unclear. The aim of the present study was to investigate the functional role and the mechanism of S1PR3 in lipopolysaccharide (LPS)‑induced human nucleus pulposus cells. The expression of S1PR3 and Toll‑like receptor (TLR) 2 in LPS‑induced nucleus pulposus (NP) cells was investigated using western blotting. The Cell Counting Kit‑8 assay was used to detect cell proliferation, and the levels of inflammatory factors were detected using ELISA. Flow cytometry and western blotting were used for the assessment of apoptosis. The deposition of extracellular matrix (ECM) proteins was investigated using reverse transcription‑quantitative PCR and western blotting. In addition, western blotting was used to investigate the protein expression levels of phosphorylated (p)‑STAT3, STAT3, p‑JNK, JNK, p‑ERK, ERK, p‑p38 and p38associated with STAT3 and MAPK signaling. S1PR3 expression was reduced, while TLR2 expression was elevated in LPS‑induced human nucleus pulposus cells (HNPC). S1PR3 overexpression increased HNPC viability, inhibited the inflammatory response and suppressed apoptosis. Meanwhile, S1PR3 overexpression regulated the expression of ECM‑related proteins. Additionally, overexpression of S1PR3 inhibited the expression of the TLR2‑regulated STAT3 and MAPK pathways in LPS‑induced HNPCs. Furthermore, TLR2 overexpression partially offset the impacts of S1PR3 overexpression on HNPC viability, apoptosis level, inflammation and as ECM degradation. In conclusion, STAT3 overexpression suppressed viability injury, the inflammatory response and the level of apoptosis and alleviated ECM protein deposition in HNPCs through the TLR2/STAT3 and TLR2/MAPK pathways, which may offer a promising candidate for the amelioration of intervertebral disc degeneration.

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