TSG-6 secreted by bone marrow mesenchymal stem cells attenuates intervertebral disc degeneration by inhibiting the TLR2/NF-κB signaling pathway

Laboratory Investigation; a Journal of Technical Methods and Pathology
Hao YangXiangrui Wang

Abstract

Inflammation has been correlated with intervertebral disc degeneration (IDD). Recent evidence suggests that TNF-α-stimulated gene 6 protein (TSG-6) secreted by bone marrow mesenchymal stem cells (BMSCs) displays a remarkable ability to inhibit inflammatory processes in a variety of diseases. However, it is unknown whether BMSCs exert their therapeutic effect against IDD by secreting TSG-6. Here we investigated the effects of BMSCs and TSG-6 on IDD and explored the possible underlying mechanisms in vitro and in vivo. We found that BMSCs and TSG-6 reduced the expression of MMP-3 and MMP-13, and increased the expression of collagen II and aggrecan in the IL-1β-treated nucleus pulposus cells (NPCs), but the protective effects of BMSCs and TSG-6 were attenuated when TSG-6 expression was silenced. We also found that the activation of the TLR2/NF-κB pathway was inhibited by BMSCs and TSG-6. The levels of IL-6 and TNF-α in the degenerated NPCs were reduced and the proliferation of IL-1β-treated NPCs was increased in the presence of BMSCs and TSG-6. Furthermore, in vivo experiments showed that BMSCs and TSG-6 restored the MRI T2-weighted signal intensity and increased collagen II and aggrecan expression in the degenerated nucleus pulpos...Continue Reading

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Citations

Apr 7, 2020·The Journal of Clinical Investigation·Thomas BuchheitRu-Rong Ji
Nov 7, 2019·International Journal of Molecular Sciences·Joan Oliva
Jan 9, 2021·Stem Cells International·Karen J Juárez-NavarroN Emmanuel Díaz-Martínez
Jan 9, 2021·Stem Cell Research & Therapy·Mesude BicerDarius Widera

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Methods Mentioned

BETA
flow cytometry
reverse transcription-PCR
transfection
protein assay
electrophoresis
enzyme-linked immunosorbent assay
fluorescence microscopy
nuclear translocation
ELISA

Software Mentioned

ImageJ
Primer
Quantity One
ARRIVE
SPSS

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