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Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_2 | Pages 39 - 39
1 Feb 2018
Humphreys M Richardson S Hoyland J
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Background. Intervertebral disc degeneration is implicated as a major cause of chronic lower back pain. Current therapies for lower back pain are aimed purely at relieving the symptoms rather than targeting the underlying aberrant cell biology. As such focus has shifted to development of cell based alternatives. Notochordal cells are progenitors to the adult nucleus pulposus that display therapeutic potential. However, notochordal cell phenotype and suitable culture conditions for research or therapeutic application are poorly described. This study aims to develop a suitable culture system to allow comprehensive study of the notochordal phenotype. Methods & Results. Porcine notochordal cells were isolated from 6 week post natal discs using dissection and enzymatic digestion and cultured in vitro under different conditions: (1)DMEM vs αMEM (2)laminin-521, fibronectin, gelatin and untreated tissue culture plastic (3)2% 02 vs normoxia (4)αMEM (300 mOsm/L) vs αMEM (400 mOsm/L). Notochordal cells were cultured in alginate beads as a control. Adherence, cell viability, morphology and expression of known notochordal markers (CD24, KRT8, KRT18, KRT19 and T) were assessed throughout the culture period. Use of αMEM media and laminin-521 coated surfaces displayed the greatest cell adherence, viability and retention of notochordal cell morphology and gene expression, which was further enhanced through culture in hypoxia and hyperosmolar media mimicking the intervertebral disc niche. Conclusions. Assessment of the therapeutic potential of notochordal cells is potentially valuable to development of a cell based therapy for chronic lower back pain. Our model has provided a system in which notochordal cells can be studied extensively. Conflicts of Interest: None. Funding obtained from the Henry Smith Charity, London


Bone & Joint Research
Vol. 12, Issue 9 | Pages 522 - 535
4 Sep 2023
Zhang G Li L Luo Z Zhang C Wang Y Kang X

Aims

This study aimed, through bioinformatics analysis and in vitro experiment validation, to identify the key extracellular proteins of intervertebral disc degeneration (IDD).

Methods

The gene expression profile of GSE23130 was downloaded from the Gene Expression Omnibus (GEO) database. Extracellular protein-differentially expressed genes (EP-DEGs) were screened by protein annotation databases, and we used Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to analyze the functions and pathways of EP-DEGs. STRING and Cytoscape were used to construct protein-protein interaction (PPI) networks and identify hub EP-DEGs. NetworkAnalyst was used to analyze transcription factors (TFs) and microRNAs (miRNAs) that regulate hub EP-DEGs. A search of the Drug Signatures Database (DSigDB) for hub EP-DEGs revealed multiple drug molecules and drug-target interactions.


Bone & Joint 360
Vol. 3, Issue 2 | Pages 32 - 65
1 Apr 2014
Adams MA

This short contribution aims to explain how intervertebral disc ‘degeneration’ differs from normal ageing, and to suggest how mechanical loading and constitutional factors interact to cause disc degeneration and prolapse. We suggest that disagreement on these matters in medico-legal practice often arises from a misunderstanding of the nature of ‘soft-tissue injuries’.


Bone & Joint Research
Vol. 2, Issue 8 | Pages 169 - 178
1 Aug 2013
Rodrigues-Pinto R Richardson SM Hoyland JA

Mesenchymal stem-cell based therapies have been proposed as novel treatments for intervertebral disc degeneration, a prevalent and disabling condition associated with back pain. The development of these treatment strategies, however, has been hindered by the incomplete understanding of the human nucleus pulposus phenotype and by an inaccurate interpretation and translation of animal to human research. This review summarises recent work characterising the nucleus pulposus phenotype in different animal models and in humans and integrates their findings with the anatomical and physiological differences between these species. Understanding this phenotype is paramount to guarantee that implanted cells restore the native functions of the intervertebral disc.

Cite this article: Bone Joint Res 2013;2:169–78.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 10 | Pages 1298 - 1304
1 Oct 2012
Hughes SPF Freemont AJ Hukins DWL McGregor AH Roberts S

This article reviews the current knowledge of the intervertebral disc (IVD) and its association with low back pain (LBP). The normal IVD is a largely avascular and aneural structure with a high water content, its nutrients mainly diffusing through the end plates. IVD degeneration occurs when its cells die or become dysfunctional, notably in an acidic environment. In the process of degeneration, the IVD becomes dehydrated and vascularised, and there is an ingrowth of nerves. Although not universally the case, the altered physiology of the IVD is believed to precede or be associated with many clinical symptoms or conditions including low back and/or lower limb pain, paraesthesia, spinal stenosis and disc herniation.

New treatment options have been developed in recent years. These include biological therapies and novel surgical techniques (such as total disc replacement), although many of these are still in their experimental phase. Central to developing further methods of treatment is the need for effective ways in which to assess patients and measure their outcomes. However, significant difficulties remain and it is therefore an appropriate time to be further investigating the scientific basis of and treatment of LBP.