Fullerol nanoparticles suppress inflammatory response and adipogenesis of vertebral bone marrow stromal cells—a potential novel treatment for intervertebral disc degeneration

Abstract Objective To investigate the potential clinical application of quantitative MRI in assessing the correlation between lumbar vertebrae bone marrow fat deposition and intervertebral disc degeneration. Materials and methods A total of 104 chronic lower-back pain volunteers underwent 3.0-T MRI with T2-weighted imaging, T2 mapping, and iterative decomposition of water and fat with echo asymmetry and least squares estimation (IDEAL-IQ) between August 2018 and June 2019. Each disc was assessed with T2 value by T2 mapping, and the L1-S1 vertebral bone marrow fat fraction was assessed by IDEAL-IQ. The differences and relationship between T2 value and the adjacent vertebral bone marrow fat fraction values within the five Pfirrmann groups, five age groups, and five lumbar levels were statistically analyzed. Results The vertebral bone marrow fat fraction had a significant negative correlation with T2 values of nucleus pulposus’ T2 values (p < 0.001). However, the significant negative correlation was only found between T2 values of nucleus pulposus and adjacent vertebral bone marrow fat in Pfirrmann II–III, L1/2-L5/S1 level, and 40–49 years’ age groups. Pfirrmann grades of the intervertebral disc were positively correlated with adjacent vertebrae bone marrow fat fraction (p < 0.05). Conclusion Lumbar bone marrow fat deposition significantly increases during the early stages of intervertebral disc degeneration. Quantitative measurements of bone marrow fat deposition and water content of intervertebral discs have a predictive value and are an important supplement to the qualitative traditional classification strategies for the early stages of intervertebral disc degeneration.

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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

10.21203/rs.3.rs-71602/v2 ◽

2020 ◽

Author(s):

Xiao Yang ◽

zhiqian chen ◽

Chen Chen ◽

Chen Han ◽

Yifan Zhou ◽

...

Keyword(s):

Bone Marrow ◽

Intervertebral Disc ◽

Signaling Pathway ◽

Histological Examination ◽

Stromal Cells ◽

Bone Marrow Stromal Cells ◽

Transforming Growth Factor ◽

Marrow Stromal Cells ◽

Cell Counting ◽

Height Loss

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: IVD from patients were gathered for histological examination. The expression of transforming growth factor beta 1 (TGF-β) 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, 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 was induced to adopt to a pro-fibrotic phenotype with increased expression fibrotic markers Col1a1, Col3a1, FSP1. The pro-fibrotic effect of Bleomycin on AF cells and BMSCs was in part due to the activation of the TGFβ-TGFβR1-SMAD2/3 signaling pathway. Pharmacological inhibition or gene knock-down of TGFβR1 could mitigate the pro-fibrotic effects. Conclusion: Locally injection of Bleomycin in rats’ IVD induced rapid fibrosis and maintained its height through TGFβ-TGFβR1-SMAD2/3 signaling pathway.

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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

Stem Cell Research & Therapy ◽

10.1186/s13287-020-02093-9 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Xiao Yang ◽

Zhiqian Chen ◽

Chen Chen ◽

Chen Han ◽

Yifan Zhou ◽

...

Keyword(s):

Bone Marrow ◽

Intervertebral Disc ◽

Signaling Pathway ◽

Histological Examination ◽

Stromal Cells ◽

Bone Marrow Stromal Cells ◽

Transforming Growth Factor ◽

Marrow Stromal Cells ◽

Cell Counting ◽

Height Loss

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-β) 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 TGFβ-TGFβR1-SMAD2/3 signaling pathway. Pharmacological inhibition or gene knock-down of TGFβR1 could mitigate the pro-fibrotic effects. Conclusion Locally, injection of bleomycin in rats’ IVD induced rapid fibrosis and maintained its height through the TGFβ-TGFβR1-SMAD2/3 signaling pathway.

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Comparison of Exosomes Secreted by Culture‐Expanded Annulus Fibrosus, Nucleus Pulposus, and Bone Marrow Stromal Cells for Intervertebral Disc Repair

The FASEB Journal ◽

10.1096/fasebj.2020.34.s1.07431 ◽

2020 ◽

Vol 34 (S1) ◽

pp. 1-1

Author(s):

Peter Linde ◽

John Kisiday ◽

Christian Puttlitz

Keyword(s):

Bone Marrow ◽

Intervertebral Disc ◽

Nucleus Pulposus ◽

Stromal Cells ◽

Bone Marrow Stromal Cells ◽

Annulus Fibrosus ◽

Marrow Stromal Cells ◽

Disc Repair ◽

Intervertebral Disc Repair

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Osteogenic differentiation of bone marrow stromal cells is hindered by the presence of intervertebral disc cells

Arthritis Research & Therapy ◽

10.1186/s13075-015-0900-2 ◽

2015 ◽

Vol 18 (1) ◽

Cited By ~ 10

Author(s):

Samantha C. W. Chan ◽

Adel Tekari ◽

Lorin M. Benneker ◽

Paul F. Heini ◽

Benjamin Gantenbein

Keyword(s):

Bone Marrow ◽

Intervertebral Disc ◽

Osteogenic Differentiation ◽

Stromal Cells ◽

Bone Marrow Stromal Cells ◽

Marrow Stromal Cells ◽

Disc Cells

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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

10.21203/rs.3.rs-71602/v1 ◽

2020 ◽

Author(s):

Xiao Yang ◽

zhiqian chen ◽

Chen Chen ◽

Chen Han ◽

Yifan Zhou ◽

...

Keyword(s):

Bone Marrow ◽

Intervertebral Disc ◽

Signaling Pathway ◽

Histological Examination ◽

Stromal Cells ◽

Bone Marrow Stromal Cells ◽

Transforming Growth Factor ◽

Marrow Stromal Cells ◽

Cell Counting ◽

Height Loss

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: IVD from patients were gathered for histological examination. The expression of transforming growth factor beta 1 (TGF-β) 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, 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 was induced to adopt to a pro-fibrotic phenotype with increased expression fibrotic markers Col1a1, Col3a1, FSP1. The pro-fibrotic effect of Bleomycin on AF cells and BMSCs was in part due to the activation of the TGFβ-TGFβR1-SMAD2/3 signaling pathway. Pharmacological inhibition or gene knock-down of TGFβR1 could mitigate the pro-fibrotic effects. Conclusion: Locally injection of Bleomycin in rats’ IVD induced rapid fibrosis and maintained its height through TGFβ-TGFβR1-SMAD2/3 signaling pathway.

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