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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


Bone & Joint Research
Vol. 12, Issue 6 | Pages 387 - 396
26 Jun 2023
Xu J Si H Zeng Y Wu Y Zhang S Shen B

Aims

Lumbar spinal stenosis (LSS) is a common skeletal system disease that has been partly attributed to genetic variation. However, the correlation between genetic variation and pathological changes in LSS is insufficient, and it is difficult to provide a reference for the early diagnosis and treatment of the disease.

Methods

We conducted a transcriptome-wide association study (TWAS) of spinal canal stenosis by integrating genome-wide association study summary statistics (including 661 cases and 178,065 controls) derived from Biobank Japan, and pre-computed gene expression weights of skeletal muscle and whole blood implemented in FUSION software. To verify the TWAS results, the candidate genes were furthered compared with messenger RNA (mRNA) expression profiles of LSS to screen for common genes. Finally, Metascape software was used to perform enrichment analysis of the candidate genes and common genes.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_2 | Pages 33 - 33
1 Feb 2018
Richardson S Rodrigues-Pinto R Hoyland J
Full Access

Background. While the human embryonic, foetal and juvenile intervertebral disc (IVD) is composed of large vacuolated notochordal cells, these morphologically distinct cells are lost with skeletal maturity being replaced by smaller nucleus pulpous cells. Notochordal cells are thought to be fundamental in maintaining IVD homeostasis and, hence, their loss in humans may be a key initiator of degeneration, leading ultimately to back pain. Therefore, it is essential to understand the human notochordal cell phenotype to enable the development of novel biological/regenerative therapies. Methods. CD24+ notochordal cells and CD24- sclerotomal cells were sorted from enzymatically-digested human foetal spines (7.5–14 WPC, n=5) using FACS. Sorting accuracy was validated using qPCR for known notochordal markers and Affymetrix cDNA microarrays performed. Differential gene expression was confirmed (qPCR) and Interactive Pathway Analysis (IPA) performed. Results. CD24+ve notochordal cells (mean 10.4%) and CD24-ve sclerotomal cells (mean 60.9% CD24-) were successfully sorted. Higher expression of notochordal markers CD24 and brachyury was identified in CD24+ve cells. Hierarchical clustering and PCA mapping revealed distinct differences in the gene expression profile of CD24+ and CD24- cells. Top notochordal markers were CD24, STMN2. RTN1, PRPH and CXCL12. IPA identified IL-1 receptor antagonist (IL-1RN) and noggin as master regulators of notochordal cell phenotype. Conclusions. This study has, for the first time, defined human foetal notochordal cell phenotype and identified important pathways and upstream regulators. In particular, IL-1RN and noggin are of interest as master regulators of notochordal cell function, suggesting vital roles for these molecules in IVD development and homeostasis. Conflicts of interest. No conflicts of interest. Sources of funding. We would like to acknowledge UKRMP Acellular Hub, MRC, NIHR Musculoskeletal BRU and The Rosetrees Trust for funding this research