Dataset Information

Bleomycin induces fibrotic transformation of bone marrow stromal cells to treat height loss of intervertebral disc through the TGF?R1/Smad2/3 pathway.

ABSTRACT:

Background

Lower back pain is often accredited to loss of intervertebral disc (IVD) height and compromised spine stability as a result of intervertebral disc degeneration (IVDD). We aim to locally use bleomycin to induce the fibrotic transformation of bone marrow stromal cells (BMSCs) as a means to induce reparative fibrosis to slow down the height loss.

Methods

IVDs from patients were gathered for histological examination. The expression of the transforming growth factor beta 1 (TGF-?) signaling pathway was determined by qPCR and western blotting. Nucleus pulposus (NP) cells, annulus fibrosus (AF) cells, and the rats' bone marrow stromal cells (BMSC) were cultured and their responsiveness to bleomycin was evaluated by Cell Counting Kit-8, comet assay, transwell migration, and wound healing assays. Rat IVDD models were created by puncture and rescued by bleomycin injection, and the effectiveness was evaluated by images (X-ray and MRI) and atomic force microscope.

Results

Histological examination showed increased levels of pro-fibrotic markers in IVDD tissues from patients. AF cells and BMSC cells were induced to adopt a pro-fibrotic phenotype with increased expression fibrotic markers Col1a1, Col3a1, and FSP1. The pro-fibrotic effect of bleomycin on AF cells and BMSCs was in part due to the activation of the TGF?-TGF?R1-SMAD2/3 signaling pathway. Pharmacological inhibition or gene knock-down of TGF?R1 could mitigate the pro-fibrotic effects.

Conclusion

Locally, injection of bleomycin in rats' IVD induced rapid fibrosis and maintained its height through the TGF?-TGF?R1-SMAD2/3 signaling pathway.

SUBMITTER: Yang X

PROVIDER: S-EPMC7791639 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Bleomycin induces fibrotic transformation of bone marrow stromal cells to treat height loss of intervertebral disc through the TGFβR1/Smad2/3 pathway.

Yang Xiao X Chen Zhiqian Z Chen Chen C Han Chen C Zhou Yifan Y Li Xunlin X Tian Haijun H Cheng Xiaofei X Zhang Kai K Qin An A Zhou Tangjun T Zhao Jie J

Stem cell research & therapy 20210107 1

<h4>Background</h4>Lower back pain is often accredited to loss of intervertebral disc (IVD) height and compromised spine stability as a result of intervertebral disc degeneration (IVDD). We aim to locally use bleomycin to induce the fibrotic transformation of bone marrow stromal cells (BMSCs) as a means to induce reparative fibrosis to slow down the height loss.<h4>Methods</h4>IVDs from patients were gathered for histological examination. The expression of the transforming growth factor beta 1 ( ...[more]

PMID: 33413668

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