scholarly journals Differential regulation of TRP channel gene and protein expression by intervertebral disc degeneration and back pain

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
A. Sadowska ◽  
W. Hitzl ◽  
A. Karol ◽  
P. Jaszczuk ◽  
H. Cherif ◽  
...  
Keyword(s):  
Gene Expression ◽  
Back Pain ◽  
Intervertebral Disc ◽  
Protein Expression ◽  
Pain Intensity ◽  
Trp Channels ◽  
Gene Array ◽  
Exact Function ◽  
Gene And Protein Expression ◽  
Ivd Degeneration

AbstractIntervertebral disc (IVD) degeneration and consequent low back pain (LBP) are common and costly pathological processes that require improved treatment strategies. Transient Receptor Potential (TRP) channels constitute a family of multimodal ion channels that have recently emerged as contributors to disc pathologies and were thus proposed as potential therapeutic targets, although limited data on their presence and function in the IVD exist. The purpose of this study was to determine the mRNA and protein expression of TRP channels in non-degenerated and degenerated human IVD tissue (with different pain intensity and chronicity) using gene array, conventional qPCR and immunohistochemistry. We could demonstrate that 26 out of 28 currently known TRP channels are expressed in the IVD on the mRNA level, thereby revealing novel therapeutic candidates from the TRPC, TRPM and TRPML subfamilies. TRPC6, TRPM2 and TRPML1 displayed enhanced gene and protein expression in degenerated IVDs as compared to non-degenerated IVDs. Additionally, the gene expression of TRPC6 and TRPML1 was influenced by the IVD degeneration grade. Pain intensity and/or chronicity influenced the gene and/or protein expression of TRPC6, TRPM2 and TRML1. Interestingly, decreased gene expression of TRPM2 was observed in patients treated with steroids. This study supports the importance of TRP channels in IVD homeostasis and pathology and their possible application as pharmacological targets for the treatment of IVD degeneration and LBP. However, the exact function and activation of the highlighted TRP channels will have to be determined in future studies.

scholarly journals Toll-like receptor 2 induced senescence in intervertebral disc cells of patients with back pain can be attenuated by o-vanillin

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Matthew Mannarino ◽  
Hosni Cherif ◽  
Li Li ◽  
Kai Sheng ◽  
Oded Rabau ◽  
...  
Keyword(s):  
Gene Expression ◽  
Back Pain ◽  
Protein Expression ◽  
Disc Degeneration ◽  
Cell Senescence ◽  
Enzyme Linked Immunosorbent Assay ◽  
Matrix Synthesis ◽  
Gene And Protein Expression ◽  
Pain Patients ◽  
In Cells

Abstract Background There is an increased level of senescent cells and toll-like teceptor-1, -2, -4, and -6 (TLR) expression in degenerating intervertebral discs (IVDs) from back pain patients. However, it is currently not known if the increase in expression of TLRs is related to the senescent cells or if it is a more general increase on all cells. It is also not known if TLR activation in IVD cells will induce cell senescence. Methods Cells from non-degenerate human IVD were obtained from spine donors and cells from degenerate IVDs came from patients undergoing surgery for low back pain. Gene expression of TLR-1,2,4,6, senescence and senescence-associated secretory phenotype (SASP) markers was evaluated by RT-qPCR in isolated cells. Matrix synthesis was verified with safranin-O staining and Dimethyl-Methylene Blue Assay (DMMB) confirmed proteoglycan content. Protein expression of p16INK4a, SASP factors, and TLR-2 was evaluated by immunocytochemistry (ICC) and/or by enzyme-linked immunosorbent assay (ELISA). Results An increase in senescent cells was found following 48-h induction with a TLR-2/6 agonist in cells from both non-degenerate and degenerating human IVDs. Higher levels of SASP factors, TLR-2 gene expression, and protein expression were found following 48-h induction with TLR-2/6 agonist. Treatment with o-vanillin reduced the number of senescent cells, and increased matrix synthesis in IVD cells from back pain patients. Treatment with o-vanillin after induction with TLR-2/6 agonist reduced gene and protein expression of SASP factors and TLR-2. Co-localized staining of p16INK4a and TLR-2 demonstrated that senescent cells have a high TLR-2 expression. Conclusions Taken together our data demonstrate that activation of TLR-2/6 induce senescence and increase TLR-2 and SASP expression in cells from non-degenerate IVDs of organ donors without degeneration and back pain and in cells from degenerating human IVD of patients with disc degeneration and back pain. The senescent cells showed high TLR-2 expression suggesting a link between TLR activation and cell senescence in human IVD cells. The reduction in senescence, SASP, and TLR-2 expression suggest o-vanillin as a potential disease-modifying drug for patients with disc degeneration and back pain.

scholarly journals Expression and activity of hyaluronidases HYAL-1, HYAL-2 and HYAL-3 in the human intervertebral disc

2019 ◽  
Vol 29 (3) ◽  
pp. 605-615 ◽  
Author(s):  
Olga Krupkova ◽  
Helen Greutert ◽  
Norbert Boos ◽  
Johannes Lemcke ◽  
Thomas Liebscher ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hyaluronic Acid ◽  
Intervertebral Disc ◽  
Protein Expression ◽  
Severe Group ◽  
Health And Disease ◽  
Catabolic Response ◽  
Donor Variation ◽  
Ivd Degeneration ◽  
Expression And Activity

Abstract Purpose Hyaluronic acid plays an essential role in water retention of the intervertebral disc (IVD) and thus provides flexibility and shock absorbance in the spine. Hyaluronic acid gets degraded by hyaluronidases (HYALs), and some of the resulting fragments were previously shown to induce an inflammatory and catabolic response in human IVD cells. However, no data currently exist on the expression and activity of HYALs in IVD health and disease. Methods Gene expression, protein expression and activity of HYALs were determined in human IVD biopsies with different degrees of degeneration (n = 50 total). Furthermore, freshly isolated human IVD cells (n = 23 total) were stimulated with IL-1β, TNF-α or H2O2, followed by analysis of HYAL-1, HYAL-2 and HYAL-3 gene expression. Results Gene expression of HYAL-1 and protein expression of HYAL-2 significantly increased in moderate/severe disc samples when compared to samples with no or low IVD degeneration. HYAL activity was not significantly increased due to high donor–donor variation, but seemed overall higher in the moderate/severe group. An inflammatory environment, as seen during IVD disease, did not affect HYAL-1, HYAL-2 or HYAL-3 expression, whereas exposure to oxidative stress (100 µM H2O2) upregulated HYAL-2 expression relative to untreated controls. Conclusion Although HYAL-1, HYAL-2 and HYAL-3 are all expressed in the IVD, HYAL-2 seems to have the highest pathophysiological relevance. Nonetheless, further studies will be needed to comprehensively elucidate its significance and to determine its potential as a therapeutic target. Graphic abstract These slides can be retrieved under Electronic Supplementary Material.

scholarly journals Influence of Angiopoietin Treatment with Hypoxia and Normoxia on Human Intervertebral Disc Progenitor Cell’s Proliferation, Metabolic Activity, and Phenotype

2021 ◽  
Vol 11 (15) ◽  
pp. 7144
Author(s):  
Muriel C. Bischof ◽  
Sonja Häckel ◽  
Andrea Oberli ◽  
Andreas S. Croft ◽  
Katharina A. C. Oswald ◽  
...  
Keyword(s):  
Gene Expression ◽  
Intervertebral Disc ◽  
Metabolic Activity ◽  
Cell Metabolism ◽  
Trauma Patients ◽  
Low Back ◽  
Relative Gene Expression ◽  
Progenitor Cell Population ◽  
Ivd Degeneration ◽  
Relative Gene

Increasing evidence implicates intervertebral disc (IVD) degeneration as a major contributor to low back pain. In addition to a series of pathogenic processes, degenerated IVDs become vascularized in contrast to healthy IVDs. In this context, angiopoietin (Ang) plays a crucial role and is involved in cytokine recruitment, and anabolic and catabolic reactions within the extracellular matrix (ECM). Over the last decade, a progenitor cell population has been described in the nucleus pulposus (NP) of the IVD to be positive for the Tie2 marker (also known as Ang-1 receptor). In this study, we investigated the influence of Ang-1 and Ang-2 on human NP cell (Tie2+, Tie2- or mixed) populations isolated from trauma patients during 7 days in normoxia (21% O2) or hypoxia (≤ 5% O2). At the end of the process, the proliferation and metabolic activity of the NP cells were analyzed. Additionally, the relative gene expression of NP-related markers was evaluated. NP cells showed a higher proliferation depending on the Ang treatment. Moreover, the study revealed higher NP cell metabolism when cultured in hypoxia. Additionally, the relative gene expression followed, with an increase linked to the oxygen level and Ang concentration. Our study comparing different NP cell populations may be the start of new approaches for the treatment of IVD degeneration.

scholarly journals 83 Spatially resolved transcriptomic and proteomic investigation of breast cancer and its immune microenvironment

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A91-A91
Author(s):  
Jennifer Chew ◽  
Cedric Uytingco ◽  
Rapolas Spalinskas ◽  
Yifeng Yin ◽  
Joe Shuga ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Tumor Microenvironment ◽  
Protein Expression ◽  
Protein Detection ◽  
Response To Therapy ◽  
Pathological Examination ◽  
Multi Drug Resistance ◽  
Spatially Resolved ◽  
Gene And Protein Expression

BackgroundThe tumor microenvironment (TME) is composed of highly heterogeneous extracellular structures and cell types such as endothelial cells, immune cells, and fibroblasts that dynamically influence and communicate with each other. The constant interaction between a tumor and its microenvironment plays a critical role in cancer development and progression and can significantly affect a tumor’s response to therapy and capacity for multi-drug resistance. High resolution analyses of gene and protein expression with spatial context can provide deeper insights into the interactions between tumor cells and surrounding cells within the TME, where a better understanding of the underlying biology can improve treatment efficacy and patient outcomes. Here, we demonstrated the ability to perform streamlined multi-omic tumor analyses by utilizing the 10X Genomics Visium Spatial Gene Expression Solution for FFPE with multiplex protein enablement. This technique simultaneously assesses gene and protein expression to elucidate the immunological profile and microenvironment of different breast cancer samples in conjunction with standard pathological methods.MethodsSerial (5 µm) sections of FFPE human breast cancer samples were placed on Visium Gene Expression (GEX) slides. The Visium GEX slides incorporate ~5,000 molecularly barcoded, spatially encoded capture spots onto which tissue sections are placed, stained, and imaged. Following incubation with a human whole transcriptome, probe-based RNA panel and an immuno-oncology oligo-tagged antibody panel, developed with Abcam conjugated antibodies, the tissues are permeabilized and the representative probes are captured. Paired GEX and protein libraries are generated for each section and then sequenced on an Illumina NovaSeq at a depth of ~50,000 reads per spot. Resulting reads from both libraries are aligned and overlaid with H&E-stained tissue images, enabling analysis of both mRNA and protein expression. Additional analyses and data visualizations were performed on the Loupe Browser v4.1 desktop software.ConclusionsSpatial transcriptomics technology complements pathological examination by combining histological assessment with the throughput and deep biological insight of highly-multiplexed protein detection and RNA-seq. Taken together, our work demonstrated that Visium Spatial technology provides a spatially-resolved, multi-analyte view of the tumor microenvironment, where a greater understanding of cellular behavior in and around tumors can help drive discovery of new biomarkers and therapeutic targets.

scholarly journals Reactive Oxygen Species Mediate Low Back Pain by Upregulating Substance P in Intervertebral Disc Degeneration

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Jiancheng Zheng ◽  
Jian Zhang ◽  
Xingkai Zhang ◽  
Zhiping Guo ◽  
Wenjian Wu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Low Back Pain ◽  
Back Pain ◽  
Substance P ◽  
Intervertebral Disc ◽  
Reactive Oxygen ◽  
Alternative Methods ◽  
Low Back ◽  
Oxygen Species ◽  
Ivd Degeneration

Reactive oxygen species (ROS) are thought to have a strong correlation with a number of intervertebral disc (IVD) diseases. Here, we aimed to determine whether ROS represent an etiology of low back pain (LBP) during IVD degeneration. Thirty degenerated intervertebral disc samples were obtained from patients, and ROS levels were quantified using dihydroethidium (DHE) staining. The results suggested a significant correlation between the ROS level and the severity of LBP. Subsequently, a puncture-induced LBP model was established in rats, and ROS levels significantly increased compared with those in the sham surgery group, accompanied with severe puncture-induced IVD degeneration. In addition, when ROS levels were increased by H2O2 administration or decreased by NAC treatment, the rats showed increased or decreased LBP, respectively. Based on this evidence, we further determined that stimulation with H2O2 in nucleus pulposus cells (NPCs) in vivo or in vitro resulted in upregulation of substance P (SP), a peptide thought to be involved in the synaptic transmission of pain, and that the severity of LBP decreased when SP levels were increased by exogenous SP administration or neutralized via aprepitant treatment in the IVDs of rats. In conclusion, ROS are primary inducers of LBP based on clinical and animal data, and the mechanism involves ROS stimulation of NPCs to secrete SP, which is a critical neurotransmitter peptide, to promote LBP in IVDs. Therefore, reducing the level of ROS with specific drugs and inhibiting SP may be alternative methods to treat LBP in the clinic.

Angiopoietin 1 and 2 gene and protein expression is differentially regulated in acute anti-Thy1.1 glomerulonephritis

2008 ◽  
Vol 294 (5) ◽  
pp. F1174-F1184 ◽  
Author(s):  
Valentina Câmpean ◽  
Britta Karpe ◽  
Christian Haas ◽  
Akram Atalla ◽  
Harm Peters ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Expression ◽  
Glomerular Injury ◽  
Double Immunofluorescence ◽  
Real Time Quantitative Pcr ◽  
Glomerular Capillary ◽  
Gene And Protein Expression ◽  
Nonradioactive In Situ Hybridization ◽  
Angiopoietin 1

Capillary neoformation is important in repair of glomerular injury of various origins. VEGF was shown to be crucial for glomerular capillary repair in glomerulonephritis (GN). We reasoned that other angiogenic factors are likewise involved in glomerular capillary remodeling and found angiopoietin 1 and -2 (ANG1 and ANG2) mRNA to be upregulated in cDNA microarrays of microdissected glomeruli of anti-Thy1.1 GN of the rat. We then studied glomerular in situ gene and protein expression of ANG1 and ANG2 and their receptor Tie-2 in the course of anti-Thy1.1 GN, which was induced by injection of OX-7 antibody. Animals were perfusion fixed at days 6 and 12 after GN induction and compared with nonnephritic controls receiving PBS. Capillary damage and repair were quantitatively analyzed using stereological techniques. Gene and protein expression of ANG1 and ANG2 and their receptor Tie-2 was analyzed using real-time quantitative PCR from microdissected glomeruli, nonradioactive in situ hybridization, double immunofluorescence, and Western blot analysis. Glomerular capillarization assessed as length density was significantly lower at day 6 of anti-Thy1.1 GN than in controls; it was back to normal values at day 12. ANG1 and ANG2 gene expression was markedly upregulated at day 6 of the disease compared with controls. Protein expression of ANG1 and ANG2 was confined to podocytes and that of Tie-2 to endothelial cells. At day 12 of anti-Thy1.1 GN when capillary restoration was nearly completed, ANG1 and ANG2 gene expression returned to basal levels, whereas Tie-2 expression was still high. With the use of a combined molecular and in situ approach, the spatial and temporal gene and protein expression of the angiopoietins and their receptor was analyzed in anti-Thy1.1 GN. The results indicate that glomerular expression of ANG1 and ANG2 and Tie-2 is differentially regulated and may contribute to healing and endothelial cell stabilization in experimental GN.

scholarly journals Comparison of the Effects of Glibenclamide on Metabolic Parameters, GLUT1 Expression, and Liver Injury in Rats With Severe and Mild Streptozotocin-Induced Diabetes Mellitus

Medicina ◽  
2012 ◽  
Vol 48 (10) ◽  
pp. 78 ◽  
Author(s):  
Jelizaveta Sokolovska ◽  
Sergejs Isajevs ◽  
Olga Sugoka ◽  
Jelena Sharipova ◽  
Natalia Paramonova ◽  
...  
Keyword(s):  
Gene Expression ◽  
Diabetes Mellitus ◽  
Protein Expression ◽  
Diabetic Rats ◽  
Metabolic Parameters ◽  
Gene And Protein Expression ◽  
Glut1 Expression ◽  
Mild Diabetes ◽  
Streptozotocin Induced Diabetes ◽  
Glut1 Gene

Background and Objective. Glucose transport via GLUT1 protein could be one of additional mechanisms of the antidiabetic action of sulfonylureas. Here, the GLUT1 gene and the protein expression was studied in rats in the course of severe and mild streptozotocin-induced diabetes mellitus and under glibenclamide treatment. Material and Methods. Severe and mild diabetes mellitus was induced using different streptozotocin doses and standard or high fat chow. Rats were treated with glibenclamide (2 mg/kg daily, per os for 6 weeks). The therapeutic effect of glibenclamide was monitored by measuring several metabolic parameters. The GLUT1 mRNA and the protein expression in the kidneys, heart, and liver was studied by means of real-time R T-PCR and immunohistochemistry. Results. The glibenclamide treatment decreased the blood glucose concentration and increased the insulin level in both models of severe and mild diabetes mellitus. Severe diabetes mellitus provoked an increase in both GLUT1 gene and protein expression in the kidneys and the heart, which was nearly normalized by glibenclamide. In the kidneys of mildly diabetic rats, an increase in the GLUT1 gene expression was neither confirmed on the protein level nor influenced by the glibenclamide treatment. In the liver of severely diabetic rats, the heart and the liver of mildly diabetic rats, the GLUT1 gene and the protein expression was changed independently of each other, which might be explained by abortive transcription, and pre- and posttranslational modifications of gene expression. Conclusions. The GLUT1 expression was found to be affected by the glucose and insulin levels and can be modulated by glibenclamide in severely and mildly diabetic rats. Glibenclamide can prevent the liver damage caused by severe hyperglycemia.

scholarly journals Preconditioning of mesenchymal stromal cells with low-intensity ultrasound: influence on chondrogenesis and directed SOX9 signaling pathways

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Neety Sahu ◽  
Gaurav Budhiraja ◽  
Anuradha Subramanian
Keyword(s):  
Gene Expression ◽  
Protein Expression ◽  
Signaling Pathways ◽  
Mesenchymal Stromal Cells ◽  
Nuclear Localization ◽  
Stromal Cells ◽  
Actin Reorganization ◽  
Low Intensity ◽  
Gene And Protein Expression ◽  
Low Intensity Ultrasound

Abstract Background Continuous low-intensity ultrasound (cLIUS) facilitates the chondrogenic differentiation of human mesenchymal stromal cells (MSCs) in the absence of exogenously added transforming growth factor-beta (TGFβ) by upregulating the expression of transcription factor SOX9, a master regulator of chondrogenesis. The present study evaluated the molecular events associated with the signaling pathways impacting SOX9 gene and protein expression under cLIUS. Methods Human bone marrow-derived MSCs were exposed to cLIUS stimulation at 14 kPa (5 MHz, 2.5 Vpp) for 5 min. The gene and protein expression of SOX9 was evaluated. The specificity of SOX9 upregulation under cLIUS was determined by treating the MSCs with small molecule inhibitors of select signaling molecules, followed by cLIUS treatment. Signaling events regulating SOX9 expression under cLIUS were analyzed by gene expression, immunofluorescence staining, and western blotting. Results cLIUS upregulated the gene expression of SOX9 and enhanced the nuclear localization of SOX9 protein when compared to non-cLIUS-stimulated control. cLIUS was noted to enhance the phosphorylation of the signaling molecule ERK1/2. Inhibition of MEK/ERK1/2 by PD98059 resulted in the effective abrogation of cLIUS-induced SOX9 expression, indicating that cLIUS-induced SOX9 upregulation was dependent on the phosphorylation of ERK1/2. Inhibition of integrin and TRPV4, the upstream cell-surface effectors of ERK1/2, did not inhibit the phosphorylation of ERK1/2 and therefore did not abrogate cLIUS-induced SOX9 expression, thereby suggesting the involvement of other mechanoreceptors. Consequently, the effect of cLIUS on the actin cytoskeleton, a mechanosensitive receptor regulating SOX9, was evaluated. Diffused and disrupted actin fibers observed in MSCs under cLIUS closely resembled actin disruption by treatment with cytoskeletal drug Y27632, which is known to increase the gene expression of SOX9. The upregulation of SOX9 under cLIUS was, therefore, related to cLIUS-induced actin reorganization. SOX9 upregulation induced by actin reorganization was also found to be dependent on the phosphorylation of ERK1/2. Conclusions Collectively, preconditioning of MSCs by cLIUS resulted in the nuclear localization of SOX9, phosphorylation of ERK1/2 and disruption of actin filaments, and the expression of SOX9 was dependent on the phosphorylation of ERK1/2 under cLIUS.

P4460microRNA-17-5p and microRNA-20a-5p downregulation by atorvastatin in Hepg2 cells: a new mechanism involved in the lipid-lowering therapy

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
K Saavedra ◽  
K Leal ◽  
D Zapata ◽  
S Sagardia ◽  
F Ortega ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Expression ◽  
Hepg2 Cells ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Ldlr Gene ◽  
Variable Effect ◽  
Incidence And Mortality ◽  
Gene And Protein Expression ◽  
In Silico Studies

Abstract Background Hypercholesterolemia increases the risk of coronary artery disease and its pharmacological treatment has demonstrated, besides reducing cholesterol levels, a decrease in the incidence and mortality from coronary events. The treatment of hypercholesterolemia is mainly driven by using statins. However, the response to pharmacological therapy shows high inter-individual variability, resulting in a variable effect in both lipid lowering and risk reduction. Thus, a better understanding of lipid-lowering mechanism and response variability at molecular level is required. Previously, we demonstrated a deregulation of microRNA (miR) profile in HepG2 cells after atorvastatin treatment, including the downregulation of miR-17-5p and miR-20a-5p which potentially targets the LDL receptor gene (LDLR), suggesting that it might be involved in allowing the LDLR overexpression on the surface of hepatic cells to subsequently capture circulating LDL and to reach the expected lipid-lowering effect. Purpose To determine the role of miR-17-5p and miR-20a-5p on the regulation of LDLR gene expression in HepG2 cells. Methods Cells HepG2 were treated with atorvastatin 10μM for 24 hours. RNA extraction and enrichment of smallRNAs were performed. The gene expression of miR-17-5p, miR-20a-5p, miR-24-3p, miR-93-5p, miR-106a-5p and LDLR were evaluated. To evaluate the effect of miR-17-5p and miR-20a-5p on LDLR gene expression, both miRs were overexpressed or repressed by transfection of mimics or inhibitors respectively into HepG2 cells for 24, 48 and 72 Hours. The gene expression of LDLR was quantified by real time PCR using RPL27 gene as reference gene. The protein expression of LDLR and beta actin were evaluated using western blot and quantified using the ImageJ software. Results Our data showed that atorvastatin significantly repressed the expression of miR-17-5p (P<0.0001) and miR-20a-5p (P=0.0456) in HepG2 cells. In silico studies showed that miR-17-5p interact with the 3'-UTR region of the LDLR. Consistently, when miR-17-5p or miR-20a-5p were overexpressed by using mimics, we observed that gene and protein expression of LDLR decreased significantly (P<0.0001 and P<0.05 respectively). Consistently, when miR-17-5p or miR-20a-5p were repressed by the use inhibitors, we observed that the gene and protein expression of LDLR increases significantly (P<0.005). Conclusions In conclusion, we demonstrate that atorvastatin induces a significant down-regulation of the miR-17-5p and miR-20a-5p in HepG2 cells. The overexpression or repression regulate the gene and protein expression of LDLR. Acknowledgement/Funding FONDECYT N°3160567, FONDECYT N°1171765 and DIUFRO DI19-0094

Mechanical Consequence of Induced Intervertebral Disc Degeneration in the SPARC-Null Mouse

2020 ◽  
Vol 143 (2) ◽  
Author(s):  
Mitchel C. Whittal ◽  
Sara Molladavoodi ◽  
Derek P. Zwambag ◽  
Magali Millecamps ◽  
Laura S. Stone ◽  
...  
Keyword(s):  
Low Back Pain ◽  
Back Pain ◽  
Intervertebral Disc ◽  
Mechanical Tests ◽  
Null Mouse ◽  
Low Back ◽  
Spine Mechanics ◽  
Tension And Compression ◽  
In Series ◽  
Ivd Degeneration

Abstract Intervertebral disc (IVD) degeneration is associated with low back pain (LBP) and accompanied by mechanical changes to the spine. Secreted protein acidic and rich in cysteine (SPARC) is a protein that contributes to the functioning and maintenance of the extracellular matrix. SPARC-null mice display accelerated IVD degeneration and pain-associated behaviors. This study examined if SPARC-null mice also display altered spine mechanics as compared to wild-type (WT) mice. Lumbar spines from SPARC-null (n = 36) and WT (n = 18) mice aged 14–25 months were subjected to cyclic axial tension and compression to determine neutral zone (NZ) length and stiffness. Three separate mechanical tests were completed for each spine to determine the effect of the number of IVDs tested in series (one versus two versus three IVDs). SPARC-null spine NZs were both stiffer (p &lt; 0.001) and smaller in length (p &lt; 0.001) than WT spines. There was an effect of the number of IVDs tested in series for NZ length but not NZ stiffness when collapsed across condition (SPARC-null and WT). Correlation analysis revealed a weak negative correlation (r = −0.24) between age and NZ length in SPARC-null mice and a weak positive correlation (r = 0.30) between age and NZ stiffness in WT mice. In conclusion, SPARC-null mice had stiffer and smaller NZs than WT mice, regardless of the number of IVDs in series being tested. The increased stiffness of these IVDs likely influences mobility at these spinal joints thereby potentially contributing to low back pain.

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