Expression of Heparanase Isoforms in Intervertebral Discs Classified According to Pfirrmann Grading System for Disc Degeneration

Rodrigues, Luciano Miller Reis; Oliveira, Lilian Zerbinatti de; Pinhal, Maria Aparecida da Silva

doi:10.1097/brs.0b013e3182894cf4

Cited by 11 publications

(10 citation statements)

References 27 publications

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“…No multiple disc levels were used in the present study. After removing the herniated disc tissue, nucleus pulposus tissues at the center of an intervertebral disc were harvested during spinal surgeries as previously reported [48, 49]. Cartilaginous endplates and annulus fibrosus tissues were discarded to ensure the identity of the nucleus pulposus tissue as much as possible [50–55].…”

Section: Methodsmentioning

confidence: 99%

Estrogen receptors involvement in intervertebral discogenic pain of the elderly women: colocalization and correlation with the expression of Substance P in nucleus pulposus

et al. 2017

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Estrogenic modulation of pain is an exceedingly complex phenomenon. However, whether estrogen is involved in discogenic low back pain still remains unclear. Here, immunoreactivity staining technique was used to examine the expression level of the estrogen receptors (ERα and ERβ) and a pain related neuropeptide, Substance P in the lumbar intervertebral discs to analyze the relationship between the ERs and Substance P. Nucleus pulposus tissues of 23 elderly female patients were harvested during spinal surgeries and made to detect the immunoreactivity staining of ERα, ERβ and Substance P. The colocalization and intensities of ERs and Substance P were explored and evaluated respectively. The correlations between changes of ERα, ERβ and Substance P were also assessed.Our results revealed that Substance P colocalized with ERα and ERβ both in cytoplasm and nucleus of the nucleus pulposus cells. HSCORE analysis indicated that Substance P negatively correlated with both ERα and ERβ expression. Collectively, the crosstalk between ERs and Substance P might exist in the disc tissue. Estrogen-dependent pain mechanism might partly be mediated through ERs and Substance P in the nucleus pulposus of the elderly females. Estrogen and its receptors might be drug targets in discogenic low back pain diseases.

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Section: Methodsmentioning

confidence: 99%

Estrogen receptors involvement in intervertebral discogenic pain of the elderly women: colocalization and correlation with the expression of Substance P in nucleus pulposus

et al. 2017

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“…Measurements of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and ribosomal protein RPL13a gene expression were used as endogenous controls, the values for sample amplification were obtained using the geometric average of both control genes. The PCR amplifications were performed using the following primer sequences, used previously in other studies by our group[ 19 , 20 ]: HPSE forward primer 5’-TGGCAAGAAGGTCTGGTTAGGAGA-3’; HPSE reverse primer 5’-GCAAAGGTGTCGGATAGCAAGGG-3’; HPSE2 forward primer 5’-CGCCTGTTAGACACACTCTCTGA-3’; HPSE2 reverse primer 5’-GTCACCACACCTTCAAGCCAA-3’; GAPDH forward primer 5’-GGAGAAGGCTGGGGCTC-3’; GAPDH reverse primer 5’-GTCCTTCCACGATACCAAAG-3’; the ribosomal protein (RPL13a) forward primer 5’-TTGAGGACCTCTGTGTATTTGTCAA-3’; and the RPL13a reverse primer 5’-CCTGGAGGAGAAGAGGAAAGAGA-3’. The post-amplification melting curve analysis was performed to confirm whether the nonspecific amplification was generated from primer-dimers.…”

Section: Methodsmentioning

confidence: 99%

The Profile of Heparanase Expression Distinguishes Differentiated Thyroid Carcinoma from Benign Neoplasms

et al. 2015

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IntroductionThe search for a specific marker that could help to distinguish between differentiated thyroid carcinoma and benign lesions remains elusive in clinical practice. Heparanase (HPSE) is an endo-beta-glucoronidase implicated in the process of tumor invasion, and the heparanase-2 (HPSE2) modulates HPSE activity. The aim of this study was to evaluate the role of heparanases in the development and differential diagnosis of follicular pattern thyroid lesions.MethodsHPSE and HPSE2 expression by qRT-PCR, immunohistochemistry evaluation, western blot analysis and HPSE enzymatic activity were evaluated.ResultsThe expression of heparanases by qRT-PCR showed an increase of HPSE2 in thyroid carcinoma (P = 0.001). HPSE activity was found to be higher in the malignant neoplasms than in the benign tumors (P<0.0001). On Western blot analysis, HPSE2 isoforms were detected only in malignant tumors. The immunohistochemical assay allowed us to establish a distinct pattern for malignant and benign tumors. Carcinomas showed a typical combination of positive labeling for neoplastic cells and negative immunostaining in colloid, when compared to benign tumors (P<0.0001). The proposed diagnostic test presents sensitivity and negative predictive value of around 100%, showing itself to be an accurate test for distinguishing between malignant and benign lesions.ConclusionsThis study shows, for the first time, a distinct profile of HPSE expression in thyroid carcinoma suggesting its role in carcinogenesis.

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“…However, heparanase-2 (HPSE2) has no enzymatic activity, but present a 30% homology with HPSE1 and its biological role still unknown. 5 , 6 …”

Section: Introductionmentioning

confidence: 99%

Studies of Molecular Changes in Intervertebral Disc Degeneration in Animal Model

et al. 2016

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Objective: To evaluate the structural and molecular changes in the extracellular matrix (ECM) during the process of intervertebral disc degeneration, using animal model. Methods: Wistar rats underwent intervertebral disc degeneration through 20-gauge needle puncture, and 360° rotation applied for 30 sec, representing the degenerated group, while control group was not submitted to this procedure. Histological parameters and expression of extracellular matrix molecules were evaluated in the 15th and 28th days after degenerative induction. Results: Fifteen days after the induction of intervertebral disc degeneration, significant changes were observed, such as reduction in the expression metalloprotease-9 (MMP9) and interleukins (IL-6 and IL-10). There was a significant increase in the expression of vascular endothelial growth factor (VEGF) and caspase-3. However, different alterations in the ECM were observed at 28 days, the level of collagen I, metalloprotease-2 (MMP2) and caspase-3 were enhanced. Furthermore, expression of heparanase isoforms (HPSE1 and HPSE2) mRNA were increased in the degenerative intervertebral disc. Conclusion: The different profiles of ECM molecules observed during the intervertebral disc degeneration suggest that molecular processes such as ECM remodeling, neovascularization, apoptosis and inflammation occur. Experimental Study.

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Expression of Heparanase Isoforms in Intervertebral Discs Classified According to Pfirrmann Grading System for Disc Degeneration

Abstract: The overexpression of HPSE1 and HPSE2 in the intervertebral degenerated discs suggests a role for these factors in mediating extracellular matrix remodeling in degenerative discs during disease development.

Cited by 11 publications

References 27 publications

Estrogen receptors involvement in intervertebral discogenic pain of the elderly women: colocalization and correlation with the expression of Substance P in nucleus pulposus

Estrogen receptors involvement in intervertebral discogenic pain of the elderly women: colocalization and correlation with the expression of Substance P in nucleus pulposus

The Profile of Heparanase Expression Distinguishes Differentiated Thyroid Carcinoma from Benign Neoplasms

Studies of Molecular Changes in Intervertebral Disc Degeneration in Animal Model

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