Pulsed electromagnetic fields reduce acute inflammation in the injured rat-tail intervertebral disc.
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ABSTRACT:
SUBMITTER: Chan AK
PROVIDER: S-EPMC6920683 | biostudies-literature | 2019 Dec
REPOSITORIES: biostudies-literature
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Pulsed electromagnetic fields reduce acute inflammation in the injured rat-tail intervertebral disc.
Chan Andrew K AK Tang Xinyan X Mummaneni Nikhil V NV Coughlin Dezba D Liebenberg Ellen E Ouyang Annie A Dudli Stefan S Lauricella Michael M Zhang Nianli N Waldorff Erik I EI Ryaby James T JT Lotz Jeffrey C JC
JOR spine 20191202 4
Pro-inflammatory cytokines are recognized contributors to intervertebral disc (IVD) degeneration and discogenic pain. We have recently reported the anti-inflammatory effect of pulsed electromagnetic fields (PEMF) on IVD cells in vitro. Whether these potentially therapeutic effects are sufficiently potent to influence disc health in vivo has not been demonstrated. We report here the effect of PEMF on acute inflammation arising from a rat-tail IVD injury model. Disc degeneration was induced by per ...[more]
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Project description:ObjectiveTo evaluate how well different magnitudes of compression-induced degenerative changes using a bent rat tail model simulated human lumbar lordosis. It has been shown that compression plays an important role in intervertebral disc degeneration (IDD).MethodsSprague-Dawley rats (n = 25) were instrumented with a special compressive apparatus that was used to bend the intervertebral disc between the 8th and the 10th caudal vertebral bodies using two Kirschner wires inserted percutaneously into the middle of two tail vertebrae. Then, rats were divided into five different static compression loads (control, sham, 1.8 N, 4.5 N, and 7.2 N). The degeneration of the discs was evaluated by magnetic resonance imaging (MRI), histology, gene expression of anabolism and catabolism after 2 weeks. We used the signal characteristics of the disc in T2-weighted MRI to reflect the changes caused by degeneration as this is the most relevant and clinically recognized way to assess IDD. Pfirrmann classification was used to classify disc images. The tail discs from C8-9 and C9-10 with their two adjacent half vertebrae were carefully cut out and decalcified. Then the sections were paraffin-embedded and cut into 5-μm sections by histotome. Finally, they were stained with Safranin O-Fast Green and hematoxylin, and hematoxylin and eosin, respectively. Images were taken using a microscope and staining and compression-induced changes were assessed by a Masuda's grading scale. The relative expression levels of mRNA encoding rat anabolic genes and catabolic genes were evaluated by real-time reverse transcription (RT)-polymerase chain reaction (PCR). The mRNA expression fold change of the target gene was calculated using the 2-ΔΔCt method in the loaded and unloaded disc.ResultsAs the loading magnitude increased, static compression produced a significantly progressive decrease in nucleus intensity on T2-weighted MRI, a decrease of aggrecan and Type II collagen, an increase in Matrix metallopeptidase-3 (MMP-3) and MMP-13 expressions, and a histomorphological degeneration. The sham group had a score of 1.4 ± 0.3, the 1.8 N group had a score of 2.4 ± 0.3, the 4.5 N group had a score of 3.2 ± 0.3, and the 7.2 N group had a score of 4.4 ± 0.3, which was based on the Pfirrmann classification score, in which the control group had a score of 1. These results demonstrated that the sham group was not significantly different from the control group. Histological analysis showed that in the loaded disc, the size of the nucleus was reduced and that the annular layer was disorganized. Based on the Masuda grading scale, scores were as follows: for the control group, 3.8 ± 0.35; sham, 4.2 ± 0.35; 1.8 N, 5.4 ± 0.35; 4.5 N, 7.6 ± 0.35; and 7.2 N, 10 ± 0.35. The gene expression was divided into the following: anabolic genes (aggrecan, collagen type1-α1, and collagen type2-α1) and catabolic genes (MMP-3 and MMP-13). Aggrecan and collagen type 2 were, respectively, downregulated from 0.42 ± 0.04 to 0.21 ± 0.04 and from 0.93 ± 0.06 to 0.17 ± 0.06 as the magnitude of compression increased, whereas collagen type 1 was significantly upregulated, from 2.49 ± 0.19 to 4.40 ± 0.19, when compared with the control group (from 1.8 to 7.2 N, P < 0.05). Catabolic genes MMP-3 and MMP-13 were significantly upregulated in all experimental groups (P < 0.05, MMP-3: from 1.46 ± 0.18 to 3.44 ± 0.18; MMP-13: from 1.19 ± 0.12 to 2.82 ± 0.13); however, MMP-13 exhibited no significant changes but tended to be upregulated when compared with the 1.8 N group with the 4.5 N group.ConclusionsDifferent stresses led to different processes of degenerative changes, the concave disc degenerating more severely as stress gradually increased.
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Project description:IntroductionA common drawback of many anticancer therapies is non-specificity in action of killing. We investigated the potential of ultra-low intensity and frequency pulsed electromagnetic fields (PEMFs) to kill breast cancer cells. Our criteria to accept this technology as a potentially valid therapeutic approach were: 1) cytotoxicity to breast cancer cells and; 2) that the designed fields proved innocuous to healthy cell classes that would be exposed to the PEMFs during clinical treatment.MethodsMCF7 breast cancer cells and their normal counterparts, MCF10 cells, were exposed to PEMFs and cytotoxic indices measured in order to design PEMF paradigms that best kill breast cancer cells. The PEMF parameters tested were: 1) frequencies ranging from 20 to 50 Hz; 2) intensities ranging from 2 mT to 5 mT and; 3) exposure durations ranging from 30 to 90 minutes per day for up to three days to determine the optimum parameters for selective cancer cell killing.ResultsWe observed a discrete window of vulnerability of MCF7 cells to PEMFs of 20 Hz frequency, 3 mT magnitude and exposure duration of 60 minutes per day. The cell damage accrued in response to PEMFs increased with time and gained significance after three days of consecutive daily exposure. By contrast, the PEMFs parameters determined to be most cytotoxic to breast cancer MCF-7 cells were not damaging to normal MCF-10 cells.ConclusionBased on our data it appears that PEMF-based anticancer strategies may represent a new therapeutic approach to treat breast cancer without affecting normal tissues in a manner that is non-invasive and can be potentially combined with existing anti-cancer treatments.
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Project description:PurposeThe purpose of this study was to determine the effect of exposure to pulsed electromagnetic fields (PEMF) on modulation of the cartilage apoptosis signalling pathway in ovariectomised rats by monitoring the expression of mRNA of X-linked inhibitor of apoptosis protein (XIAP) and Bax.MethodsForty-eight female Sprague-Dawley rats (250 ± 50 g) were randomly assigned to one of four groups: ovariectomy with PEMF treatment (PEMF group), ovariectomy with oestradiol (E2) treatment (oestrogen group), ovariectomy control (OVX group) and sham group. The ovariectomy model was prepared by surgical resection of the ovaries. After a three-month intermission, animals in the PEMF and oestrogen groups received treatment for 30 days; then serum 17β-oestradiol levels, chondrocyte morphology, and XIAP and Bax mRNA expression in knee joint cartilage were analysed.ResultsThe results showed different chondrocyte formation in each group. Serum E2 content in the PEMF and oestrogen groups was significantly higher than in the OVX group (p < 0.05). The expression of XIAP mRNA in the PEMF and oestrogen groups was significantly up-regulated compared to the OVX group, while that of Bax mRNA was significantly down-regulated (p < 0.05). The correlation between E2 level and expression of Bax mRNA was positive (0.506) and statistically significant (p < 0.001).ConclusionThese data demonstrate that PEMF can up-regulate XIAP mRNA expression and down-regulate Bax mRNA expression in ovariectomised rats. Changes in XIAP and Bax mRNA expression may be the mechanism by which PEMF therapy affects postmenopausal osteoarthritis.
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Project description:Intervertebral disc (IVD) degeneration is a multifactorial pathological process associated with low back pain, the leading cause of years lived in disability worldwide. Key characteristics of the pathological changes connected with degenerative disc disease (DDD) are the degradation of the extracellular matrix (ECM), apoptosis and senescence, as well as inflammation. The impact of nonphysiological mechanical stresses on IVD degeneration and inflammation, the mechanisms of mechanotransduction, and the role of mechanosensitive miRNAs are of increasing interest. As post-transcriptional regulators, miRNAs are known to affect the expression of 30% of proteincoding genes and numerous intracellular processes. The dysregulation of miRNAs is therefore associated with various pathologies, including degenerative diseases such as DDD. This review aims to give an overview of the current status of miRNA research in degenerative disc pathology, with a special focus on the involvement of miRNAs in ECM degradation, apoptosis, and inflammation, as well as mechanobiology.
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