Abstract
BackgroundLower 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.MethodsIVDs 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.ResultsHistological 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.ConclusionLocally, injection of bleomycin in rats’ IVD induced rapid fibrosis and maintained its height through the TGFβ-TGFβR1-SMAD2/3 signaling pathway.
Highlights
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 investigated the potential use of bleomycin to induce reparative fibrosis as a means to maintain intervertebral disc height, and we tried to use it to induce the fibrosis phenotype of bone marrow stromal cells (BMSCs) and offer an alternative treatment in degeneration caused height loss
Intervertebral disc degeneration correlates with fibrotic changes in nucleus pulposus (NP) in patients with lumbar disc herniation or degenerative lumbar spondylolisthesis Degenerative and fibrotic changes in the intervertebral discs from 12 patients with lumbar disc herniation (LDH) or degenerative lumbar spondylolisthesis (DLS) were examined by Magnetic resonance imaging (MRI) and Safranin O-Fast Green (SOFG) histological staining (Fig. 1a–c)
Summary
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). Continued dehydration results in the collapse of the NP, loss of intervertebral disc height, and the gradual loss of NP-AF borders progressing to complete degeneration of the entire intervertebral disc. This causes spine instability and nerve root compression evoking chronic back pain [4, 5]. From a different perspective that a former approach of our studies by injection of autologous dermal fibroblast cells into degenerative intervertebral to treat IVDD [17], we showed that the induction of reparative fibrosis combined with two essential cells in discs, one is to induce the fibrotic phenotype of MSCs and the other is to promote the fibroblastic-like cell AF cells
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