Research Paper Volume 11, Issue 22 pp 10252—10265
Metformin decreases LPS-induced inflammatory response in rabbit annulus fibrosus stem/progenitor cells by blocking HMGB1 release
- 1 Department of Spine Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
- 2 Department of Sports Medicine, Shanghai Sixth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200233, China
- 3 Department of Spinal Surgery, Shanghai East Hospital, Tongji University, School of Medicine, Shanghai 200120, China
received: May 7, 2019 ; accepted: November 7, 2019 ; published: November 26, 2019 ;https://doi.org/10.18632/aging.102453
How to Cite
Copyright © 2019 Han et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The present study aimed to investigate the mechanism of intervertebral disc degeneration (IVDD) and identify an efficient treatment for low back pain. Rabbit annulus fibrosus stem cells (AFSCs) were treated with metformin and lipopolysaccharide (LPS). The results indicated that LPS induced HMGB1 release from the nuclei of AFSCs and caused cell senescence in a concentration-dependent manner. The production of PGE2 and HMGB1 was increased in the medium of the LPS-treated AFSCs. Certain inflammation-associated genes (IL-β1, IL-6, COX-2 and TNF-α) and proteins (IL-β1, COX-2 and TNF-α) and specific catabolic genes (MMP-3 and MMP-13) exhibited increased expression in LPS-treated AFSCs. However, the expression levels of other anabolic genes, such as collagen I and collagen II were decreased in LPS-treated AFSCs. Following addition of metformin to LPS-containing medium, HMGB1 was retained in the nuclei of AFSCs and the production of PGE2 and HMGB1 was reduced. The expression levels of the catabolic genes and proteins were decreased and those of the anabolic genes were increased. The findings indicated that metformin exerted an anti-inflammatory effect by blocking the HMGB1 translocation and by inhibiting catabolic production and cell senescence in AFSCs. Therefore, metformin may be used as an efficient treatment for the disc degenerative disease.