scholarly journals circSPG21 protects against intervertebral disc disease by targeting miR-1197/ATP1B3

Author(s):  
Yizhen Huang ◽  
Zhenlei Zhang ◽  
Jianle Wang ◽  
Shuying Shen ◽  
Teng Yao ◽  
...  

AbstractThe abnormal expression of circular RNAs (circRNAs) is associated with numerous human diseases. This study investigated the mechanism by which circRNA acts as competitive endogenous RNA in the regulation of degenerative intervertebral disc disease (IVDD). Decreased expression of circSPG21 was detected in degenerated nucleus pulposus cells (NPCs), the function of circSPG21 in NPCs was explored and verified, and the downstream target of circSPG21 was investigated. The interaction between circSPG21 and miR-1197 and its target gene (ATP1B3) was studied by online database prediction and molecular biological verification. Finally, the circSPG21/miR-1197/ATP1B3 axis was verified in the mouse tail-looping model. The expression of circSPG21 in the nucleus pulposus in IVDD was directly related to an imbalance of anabolic and catabolic factors, which affected cell senescence. circSPG21 was found to play a role in human NPCs by acting as a sponge of miR-1197 and thereby affecting ATP1B3. The regulation of circSPG21 provides a potentially effective therapeutic strategy for IVDD.

Epigenomics ◽  
2020 ◽  
Vol 12 (13) ◽  
pp. 1095-1108
Author(s):  
Guoyong Xu ◽  
Chong Liu ◽  
Jie Jiang ◽  
Tuo Liang ◽  
Chaojie Yu ◽  
...  

Aim: To identify a key competitive endogenous RNA network for intervertebral disc degeneration. Materials & methods: Based on circular RNA, microRNA and mRNA expression profiles of nucleus pulposus cells, a variety of bioinformatics methods were used to screen key molecular structures and construct competitive endogenous RNA networks. Results: 190 upregulated genes and 77 downregulated genes were identified. Gene ontology/Kyoto Encyclopedia of Genes and Genomes functional analysis showed that autophagy was out of balance with apoptosis. Nine hub genes, five hub microRNAs and eight hub circular RNAs were obtained through progressive reverse prediction and verification. Conclusion: We believe that disc degeneration is caused by an imbalance between autophagy and apoptosis in nucleus pulposus cells, which may provide nonsurgical treatment for the future delay or prevention of spinal degenerative diseases associated with intervertebral disc degeneration.


2018 ◽  
Vol 22 (11) ◽  
pp. 5539-5551 ◽  
Author(s):  
Kaori Suyama ◽  
Daisuke Sakai ◽  
Noriaki Hirayama ◽  
Yoshihiko Nakamura ◽  
Erika Matsushita ◽  
...  

2016 ◽  
Vol 44 (1) ◽  
pp. 4
Author(s):  
Rafael Oliveira Chaves ◽  
Bruna Copat ◽  
Diego Vilibaldo Beckmann ◽  
João Pedro Scusssel Feranti ◽  
Marília Teresa De Oliveira ◽  
...  

Background: Intervertebral disc disease is a usual neurological disorder in dogs, which the spinal cord is compressed by intervertebral disc extrusion or protrusion. Fibrocartilaginous embolic myelopathy isan acute infarction disease of spinal cord caused by fibrocartilaginous emboli histologically identical to the nucleus pulposus of intervertebral discs. The aim of this report is present two cases of fibrocartilaginous embolic myelopathy in dogs with intervertebral disc disease.Cases: Two dogs - dachshund breed - were referred to the Veterinary Medical Teaching Hospital of the UFSM. In the first case, the dog was three years old and the owner described complete inability to move the pelvic limbs. The neurological examination revealed paraplegia, postural reactions deficits, normal spinal reflexes and muscle tonus in the hind limbs, pain on palpation in T12-T11 region and loss of deep pain in hind limbs. In the other case, the dog was seven years old and the owner described partial inability to move four limbs. The neurological examination revealed non-ambulatory tetraparesis, postural reactions deficit, normal spinal reflexes in four limbs and pain on palpation in cervical spine. In both cases, the presumptive diagnosis was intervertebral disc disease and surgical treatment was indicated. The dog with thoracolumbar injury died during the anesthesia and the dog with cervical injury was euthanized, after decision of owner. During the necropsy was observed intervertebral disc extrusion between L1-L2 vertebrae in a dog and between C3-C4 vertebrae in the other case with cartilaginous fragments in the spinal canal. Histopathology revealed marked diffuse necrosis with multifocal hemorrhage and cartilaginous emboli.Discussion: Fibrocartilaginous embolic myelopathy is commonly reported in large and giant breed dogs, though also occur in small and medium-sized breeds of dogs. One hypothesis is the pulpous nucleus remains soft for a longer period in large breed dogs, empowering to infiltration in the spinal cord vessels. The intervertebral disc extrusion occurs predominantly in dogs with age between three and six years old, in the cervical, thoracolumbar (T11-L3) and lumbar regions. Chondroid or fibroid degeneration of the intervertebral disc is the most common cause of spinal cord compression in small animals. In chondrodistrophic breed dogs is frequently chondroid degeneration, which the nucleus pulposus moves into the spinal canal through rupture of the annulus fibrosus (extrusion or Hansen type I), causing acute spinal cord compression. The prevalence of fibrocartilaginous embolism in adult and old dogs increase the possibility of predisposing factors, facilitating the injection intravascular of nucleus pulposus material. One of the most accepted theories about the mechanism of fibrocartilaginous emboli into the vessels is due to increase of inside discal pressure and liberation of fibrocartilaginous emboli from nucleus pulposus into the vertebral artery for retrograde flow, reaching the spinal cord by blood flow. The simultaneous occurrence of intervertebral disc disease and the infarction of spinal cord in the proximate region accentuate the hypothesis that the etiology of fibrocartilaginous embolic myelopathy is mechanical into the vessels of the spinal cord.Keywords: neurology, spinal cord, intervertebral disc disease, dogs.


Author(s):  
Ronaldo C. da Costa ◽  
Steven De Decker ◽  
Melissa J. Lewis ◽  
Holger Volk ◽  

Imaging is integral in the diagnosis of canine intervertebral disc disease (IVDD) and in differentiating subtypes of intervertebral disc herniation (IVDH). These include intervertebral disc extrusion (IVDE), intervertebral disc protrusion (IVDP) and more recently recognized forms such as acute non-compressive nucleus pulposus extrusion (ANNPE), hydrated nucleus pulposus extrusion (HNPE), and intradural/intramedullary intervertebral disc extrusion (IIVDE). Many imaging techniques have been described in dogs with roles for survey radiographs, myelography, computed tomography (CT), and magnetic resonance imaging (MRI). Given how common IVDH is in dogs, a thorough understanding of the indications and limitations for each imaging modality to aid in diagnosis, treatment planning and prognosis is essential to successful case management. While radiographs can provide useful information, especially for identifying intervertebral disc degeneration or calcification, there are notable limitations. Myelography addresses some of the constraints of survey radiographs but has largely been supplanted by cross-sectional imaging. Computed tomography with or without myelography and MRI is currently utilized most widely and have become the focus of most contemporary studies on this subject. Novel advanced imaging applications are being explored in dogs but are not yet routinely performed in clinical patients. The following review will provide a comprehensive overview on common imaging modalities reported to aid in the diagnosis of IVDH including IVDE, IVDP, ANNPE, HNPE, and IIVDE. The review focuses primarily on canine IVDH due to its frequency and vast literature as opposed to feline IVDH.


1975 ◽  
Vol 42 (4) ◽  
pp. 389-396 ◽  
Author(s):  
Bernard J. Sussman

✓ The author reviews laboratory and clinical reports that lead him to believe that chymopapain does not specifically dissolve the nucleus pulposus and is toxic for vascular and neural tissue.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yizhen Huang ◽  
Jun Gao ◽  
Jianle Wang ◽  
Huali Ye ◽  
Teng Yao ◽  
...  

AbstractThe molecular mechanism underlying the development of intervertebral disc disease (IVDD) is not completely understood. Circular RNAs (circRNAs) play a significant role in the occurrence and development of various diseases, and studies have shown that circPKNOX1 is involved in the compensatory response of extracellular matrix synthesis and secretion of the nucleus pulposus (NP) cells. However, the mechanism through which circRNAs regulate IVDD progression remains unclear; therefore, in this study, we explored the significance of circPKNOX1 in IVDD. The expression of circRNAs in NP cells of normal and degenerative patients was detected using microarray analysis, and the role of circPKNOX1 in IVDD was confirmed using RT-qPCR. The interaction networks of circRNAs, miRNAs, and miRNA target genes were detected using bioinformatics analysis, RNA fluorescence in situ hybridization, and immunofluorescence analysis. We found that the expression of circPKNOX1 decreased in IVDD cells. The expression of circPKNOX1 in NP cells, observed using RT-qPCR and western blotting, was consistent with that observed using array screening. Overexpression of circPKNOX1 increased the expression of collagen II, aggrecan, and SOX9 and decreased that of ADAMTS4, ADAMTS-5, MMP3, and MMP13. We further demonstrated that circPKNOX1 played the role of a sponge by competitively binding miR-370-3p to reverse the inhibition of KIAA0355 expression. Our findings indicated that circPKNOX1 affected the progression of IVDD by regulating the expression of KIAA0355 via miR-370-3p. Therefore, circPKNOX1-based therapy may serve as an effective IVDD treatment strategy.


2015 ◽  
Vol 5 (1_suppl) ◽  
pp. s-0035-1554146-s-0035-1554146
Author(s):  
Kathryn S. E. Cheah ◽  
Tiffany Au ◽  
Ben Niu ◽  
Danny Chan ◽  
Michael Q. Zhang

2021 ◽  
pp. 1098612X2110280
Author(s):  
Kayla M Fowler ◽  
Theresa E Pancotto ◽  
Stephen R Werre ◽  
Michaela J Beasley ◽  
William Kay ◽  
...  

Objectives The aim of this study was to evaluate the outcome and prognosis of thoracolumbar feline intervertebral disc disease (IVDD) treated by surgical decompression. Methods This was a multi-institutional retrospective study evaluating the age, breed, sex, body weight, presenting complaint, neuroanatomic diagnosis at presentation, diagnostic imaging results, surgery performed and the overall outcome at discharge and at recheck. Bivariable associations between variables were assessed using the Kruskal–Wallis test (age and grade of IVDD at presentation) and Fisher’s exact test (grade of IVDD at presentation and outcome). Results A total of 35 cats met the inclusion criteria for the study. The most frequently reported clinical sign was difficulty walking (54.2%). The majority of cats presented with an L4–S3 localization (57%). The most common site of intervertebral disc herniation (IVDH) was at L6–L7 (34%). The majority of feline patients that received surgery had a positive outcome at the time of discharge (62.5%; n = 20/32) and at the time of the 2-week recheck (91.3%; n = 21/23). No association was identified between the age of the patient and the grade of IVDD. No association was identified between the presenting grade of IVDD and the clinical outcome at the time of discharge or at the time of recheck evaluation. Conclusions and relevance Cats undergoing spinal decompressive surgery for thoracolumbar IVDH appear to have a favorable prognosis independent of the initial presenting grade of IVDD. A larger sample size and a longer length of follow-up is necessary to obtain statistical associations between the presenting grade of IVDD and overall clinical outcome.


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