Abstract
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.
Highlights
Low back pain is a very common disc disease with a tremendous socio-economic impact
In order to study the cellular and molecular pathway of disc degeneration, stem cells were initially isolated from rabbit annulus fibrosus (AF) tissues (AFSCs) and the stemness of these annulus fibrosus stem cells (AFSCs) was identified by three stem cell markers, namely octamer-binding transcription factor-4 (Oct-4), stage-specific embryonic antigen-4 (SSEA-4) and nucleostemin (NS)
In order to study the mechanisms of intervertebral disc degeneration (IVDD) and identify an efficient approach for low back pain treatment, rabbit AF stem cells were treated with metformin and LPS
Summary
Low back pain is a very common disc disease with a tremendous socio-economic impact. More than 70% of the worldwide population has encountered low back pain during various stages of life [1]. The disease severity is more common in aging populations [1]. An efficient treatment for low back pain has not been developed, while the etiology of this disease is largely unknown. The intervertebral disc degeneration (IVDD) is a widely accepted cause of low back pain [2]. It is believed that certain inflammatory mediators are associated with herniated and degenerated intervertebral disc diseases. In vitro studies have shown that IL-6, IL-8 www.aging-us.com and PGE2 levels were increased in human intervertebral disc tissues following lipopolysaccharide (LPS) stimulation [3]. The precise cellular and molecular mechanism of IVDD is not clear [2, 4, 5]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
