The Upregulation of COX2 in Human Degenerated Nucleus Pulposus: The Association of Inflammation with Intervertebral Disc Degeneration

Intervertebral disc degeneration (IVDD) is an important risk factor of low back pain. We previously found upregulated markers of fibrosis, the late stage of chronic inflammation, in degenerated IVD with a small number of clinical specimens. Here, we aimed to study on a larger scale the association of cyclooxygenase 2 (COX2), an inflammation and/or pain marker, with IVDD. This study involved 107 LBP participants. The IVD degeneration level was graded on a 1–5 scale according to the Pfirrmann classification system. Discs at grades 1-3 were further grouped as white discs with grades 4-5 as black discs. We recorded baseline information about age, gender, body mass index (BMI), diabetes history, smoking history, and magnetic resonance imaging (MRI). Their association with IVDD was statistically analyzed. The expression level of COX2 was investigated by immunohistochemistry. The total integrated COX2 optical density (IOD), number of COX2-positive cells, and total cell number of each image were counted and analyzed by Image-Pro Plus software. The IOD and number of COX2-positive cells were divided by the total cell number to obtain COX2 expression density (IOD/cell) and COX2 positivity (cell+/cell). As a result, among the baseline information investigated, only age was found to have a significant association with IVDD. The IOD/cell was found to be significantly increased from grade 2 to grade 5, as well as in black discs compared to white discs. The cell+/cell displayed the same trend that it increased in highly degenerative discs compared to their counterparts. In conclusion, the expression of COX2 is associated with IVDD, which highlights COX2 as a biomarker for IVD degeneration and indicates the involvement of inflammation and pain signaling in IVDD.

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The Myth of Fibroid Degeneration in the Canine Intervertebral Disc: A Histopathological Comparison of Intervertebral Disc Degeneration in Chondrodystrophic and Nonchondrodystrophic Dogs

Veterinary Pathology ◽

10.1177/0300985817726834 ◽

2017 ◽

Vol 54 (6) ◽

pp. 945-952 ◽

Cited By ~ 10

Author(s):

Tove Hansen ◽

Lucas A. Smolders ◽

Marianna A. Tryfonidou ◽

Björn P. Meij ◽

Johannes C. M. Vernooij ◽

...

Keyword(s):

Intervertebral Disc ◽

Nucleus Pulposus ◽

Disc Degeneration ◽

Intervertebral Disc Degeneration ◽

Histopathological Changes ◽

Seminal Work ◽

Notochordal Cells ◽

Tissue Changes ◽

Chondroid Metaplasia ◽

Ivd Degeneration

Since the seminal work by Hans-Jörgen Hansen in 1952, it has been assumed that intervertebral disc (IVD) degeneration in chondrodystrophic (CD) dogs involves chondroid metaplasia of the nucleus pulposus, whereas in nonchondrodystrophic (NCD) dogs, fibrous metaplasia occurs. However, more recent studies suggest that IVD degeneration in NCD and CD dogs is more similar than originally thought. Therefore, the aim of this study was to compare the histopathology of IVD degeneration in CD and NCD dogs. IVDs with various grades of degeneration (Thompson grade I–III, n = 7 per grade) from both CD and NCD dogs were used (14 CD and 18 NCD dogs, 42 IVDs in total). Sections were scored according to a histological scoring scheme for canine IVD degeneration, including evaluation of the presence of fibrocyte-like cells in the nucleus pulposus. In CD dogs, the macroscopically non-degenerated nucleus pulposus contained mainly chondrocyte-like cells, whereas the non-degenerated nucleus pulposus of NCD dogs mainly contained notochordal cells. The histopathological changes in degenerated discs were similar in CD and NCD dogs and resembled chondroid metaplasia. Fibrocytes were not seen in the nucleus pulposus, indicating that fibrous degeneration of the IVD was not present in any of the evaluated grades of degeneration. In conclusion, intervertebral disc degeneration was characterized by chondroid metaplasia of the nucleus pulposus in both NCD and CD dogs. These results revoke the generally accepted concept that NCD and CD dogs suffer from a different type of IVD degeneration, in veterinary literature often referred to as chondroid or fibroid degeneration, and we suggest that chondroid metaplasia should be used to describe the tissue changes in the IVD in both breed types.

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Mesenchymal Stem Cell for Prevention and Management of Intervertebral Disc Degeneration

Stem Cells International ◽

10.1155/2012/921053 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 8

Author(s):

Umile Giuseppe Longo ◽

Nicola Papapietro ◽

Stefano Petrillo ◽

Edoardo Franceschetti ◽

Nicola Maffulli ◽

...

Keyword(s):

Intervertebral Disc ◽

Disc Degeneration ◽

Annulus Fibrosus ◽

Intervertebral Disc Degeneration ◽

Surgical Intervention ◽

Pathological Condition ◽

Treatment Strategies ◽

Clinical Applications ◽

Ivd Degeneration

Intervertebral disc degeneration (IVD) is a frequent pathological condition. Conservative management often fails, and patients with IVD degeneration may require surgical intervention. Several treatment strategies have been proposed, although only surgical discectomy and arthrodesis have been proved to be predictably effective. The aim of biological strategies is to prevent and manage IVD degeneration, improve the function, the anabolic and reparative capabilities of the nucleus pulposus and annulus fibrosus cells, and inhibit matrix degradation. At present, clinical applications are still in their infancy. Further studies are required to clarify the role of mesenchymal stem cells and gene therapy for the prevention and treatment of IVD degeneration.

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Growth Factors and Anticatabolic Substances for Prevention and Management of Intervertebral Disc Degeneration

Stem Cells International ◽

10.1155/2012/897183 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9

Author(s):

Umile Giuseppe Longo ◽

Stefano Petrillo ◽

Edoardo Franceschetti ◽

Nicola Maffulli ◽

Vincenzo Denaro

Keyword(s):

Growth Factors ◽

Intervertebral Disc ◽

Disc Degeneration ◽

Annulus Fibrosus ◽

Intervertebral Disc Degeneration ◽

Surgical Intervention ◽

Treatment Strategies ◽

Clinical Applications ◽

Ivd Degeneration

Intervertebral disc (IVD) degeneration is frequent, appearing from the second decade of life and progressing with age. Conservative management often fails, and patients with IVD degeneration may need surgical intervention. Several treatment strategies have been proposed, although only surgical discectomy and arthrodesis have been proved to be predictably effective. Biological strategies aim to prevent and manage IVD degeneration, improving the function and anabolic and reparative capabilities of the nucleus pulposus and annulus fibrosus cells and inhibiting matrix degradation. At present, clinical applications are still in their infancy. Further studies are required to clarify the role of growth factors and anticatabolic substances for prevention and management of intervertebral disc degeneration.

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Faculty Opinions recommendation of Novel function of TWEAK in inducing intervertebral disc degeneration.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1095070.550070 ◽

2007 ◽

Author(s):

Helen Gruber

Keyword(s):

Intervertebral Disc ◽

Disc Degeneration ◽

Intervertebral Disc Degeneration

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INTERVERTEBRAL DISC DEGENERATION LINKED TO STRUCTURAL GENE VARIATIONS

Pakistan Journal of Medicine and Dentistry ◽

10.36283/pjmd8-4/012 ◽

2019 ◽

Author(s):

Saeeda Baig

Keyword(s):

Intervertebral Disc ◽

Disc Degeneration ◽

Intervertebral Disc Degeneration ◽

English Language ◽

Tandem Repeats ◽

Lumbar Disc ◽

Disease Process ◽

Nucleotide Polymorphisms ◽

Structural Protein ◽

Lumbar Disc Degeneration

During the recent past focus has shifted from identifying intervertebral disc degeneration as being caused by physical exposure and strain to being linked with a variety of genetic variations. The objective of this review is to provide an up to date review of the existing research data regarding the relation of intervertebral disc degeneration to structural protein genes and their polymorphisms and thus help clearly establish further avenues where research into causation and treatment is needed. A comprehensive search using the keywords “Collagen”, “COL”, “Aggrecan”, “AGC”, “IVDD”, “intervertebral disc degeneration”, and “lumbar disc degeneration” from PubMed and Google Scholar, where literature in the English language was selected spanning from 1991 to 2019. There are many genes involved in the production of structural components of an intervertebral disc. The issues in production of these components involve the over-expression or under-expression of their genes, and single nucleotide polymorphisms and variable number of tandem repeats affecting their structures. These structural genes include primarily the collagen and the aggrecan genes. While genetic and environmental factors all come into play with a disease process like disc degeneration, the bulk of research now shows the significantly larger impact of hereditary over exposure. While further research is needed into some of the lesser studied genes linked to IVDD and also the racial variations in genetic makeup, the focus in the near future should be on establishment of genetic testing to identify individuals at greater risk of disease and deliberation regarding the use of gene therapy to prevent disc degeneration.

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