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Published on: May 24, 2017
Caspase 3 as a therapeutic target for regulation of intervertebral disc degeneration in rabbits
1Department of Advanced Medicine for Spine and Spinal Cord Disorders, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan. hidekisudo@yahoo.co.jp
Objective:
Although the etiology of intervertebral disc degeneration is poorly understood, one possible approach for its regulation is apoptosis inhibition. This study was undertaken to investigate the antiapoptotic effects of caspase 3 in intervertebral disc degeneration in rabbits.
Methods:
We investigated the effects of caspase 3 small interfering RNA (siRNA) on rabbit nucleus pulposus cells in a serum-starved medium. The effects of direct injection of Alexa Fluor 555-labeled caspase 3 siRNA into the intervertebral disc were also determined in vivo using the rabbit anular needle puncture model.
Results:
Rabbit nucleus pulposus cells transfected with caspase 3 siRNA showed a significant decrease in serum-starved apoptotic cells. After local injection of caspase 3 siRNA into intervertebral discs, red fluorescence was observed in the nucleus pulposus upon treatment with Alexa Fluor 555-labeled caspase 3 siRNA. Caspase 3 messenger RNA and protein were down-regulated in the caspase 3 siRNA group. Magnetic resonance imaging and histologic evaluation showed that degenerative changes were significantly suppressed in the caspase 3 siRNA group 4 and 8 weeks after injection. Quantification of TUNEL staining showed that the caspase 3 siRNA group had significantly fewer apoptotic nucleus pulposus cells than the control siRNA group.
Conclusion:
Our findings indicate that caspase 3 knockdown in rabbit intervertebral disc cells is effective in preventing apoptotic cell death, thus regulating intervertebral disc degeneration.
Insights
Inhibiting caspase 3 (an enzyme involved in cell death) through small interfering RNA (siRNA) effectively reduced apoptosis in rabbit intervertebral disc cells, offering a potential treatment for disc degeneration.
Area of Science:
- Biomedical Research
- Cell Biology
- Regenerative Medicine
Background:
- Intervertebral disc degeneration (IDD) is a significant cause of back pain.
- The precise mechanisms driving IDD are not fully understood.
- Apoptosis, or programmed cell death, is implicated in the progression of IDD.
Purpose of the Study:
- To investigate the potential of inhibiting caspase 3 to regulate apoptosis in the context of intervertebral disc degeneration.
- To assess the antiapoptotic effects of caspase 3 small interfering RNA (siRNA) in a rabbit model of IDD.
Main Methods:
- Rabbit nucleus pulposus cells were treated with caspase 3 siRNA in a serum-starved environment.
- Alexa Fluor 555-labeled caspase 3 siRNA was injected into the intervertebral discs of rabbits using an anular needle puncture model.
- Caspase 3 messenger RNA (mRNA) and protein levels were quantified.
- Degenerative changes were evaluated using magnetic resonance imaging (MRI) and histology.
- Apoptosis was assessed via TUNEL staining.
Main Results:
- Caspase 3 siRNA transfection significantly reduced apoptosis in rabbit nucleus pulposus cells.
- In vivo studies confirmed successful delivery and knockdown of caspase 3 mRNA and protein in the intervertebral discs.
- MRI and histological analyses revealed significant suppression of degenerative changes in the caspase 3 siRNA group.
- TUNEL staining demonstrated a marked decrease in apoptotic nucleus pulposus cells in the siRNA-treated group compared to controls.
Conclusions:
- Caspase 3 knockdown is an effective strategy to inhibit apoptotic cell death in intervertebral disc cells.
- Targeting caspase 3 presents a promising therapeutic avenue for managing intervertebral disc degeneration.
