Research Papers: Pathology:

Class 3 semaphorins expression and association with innervation and angiogenesis within the degenerate human intervertebral disc

Abbie L.A. Binch _, Ashley A. Cole, Lee M. Breakwell, Anthony L.R. Michael, Neil Chiverton, Laura B. Creemers, Alison K. Cross and Christine L. Le Maitre

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Oncotarget. 2015; 6:18338-18354. https://doi.org/10.18632/oncotarget.4274

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Abbie L. A. Binch1, Ashley A. Cole2, Lee M. Breakwell2, Anthony L. R. Michael2, Neil Chiverton2, Laura B. Creemers3, Alison K. Cross1, Christine L. Le Maitre1

1Sheffield Hallam University, Sheffield, South Yorkshire, United Kingdom

2Sheffield Teaching Hospitals, Sheffield, South Yorkshire, United Kingdom.

3Universitair Medisch Centrum, Orthopaedics Department, Utrecht, Netherlands

Correspondence to:

Christine Le Maitre, e-mail: [email protected]

Keywords: Pathology Section, intervertebral disc, cytokines, semaphorins, innervation, angiogenesis

Received: February 27, 2015     Accepted: June 03, 2015     Published: June 15, 2015


Nerve and blood vessel ingrowth during intervertebral disc degeneration, is thought to be a major cause of low back pain, however the regulation of this process is poorly understood. Here, we investigated the expression and regulation of a subclass of axonal guidance molecules known as the class 3 semaphorins, and their receptors; plexins and neuropilins within human NP tissue and their regulation by pro-inflammatory cytokines. Importantly this determined whether semaphorin expression was associated with the presence of nerves and blood vessels in tissues from human intervertebral discs. The study demonstrated that semaphorin3A, 3C, 3D, 3E and 3F and their receptors were expressed by native NP cells and further demonstrated their expression was regulated by IL-1β but to a lesser extent by IL-6 and TNFα. This is the first study to identify sema3C, sema3D and their receptors within the nucleus pulposus of intervertebral discs. Immunopositivity shows significant increases in semaphorin3C, 3D and their receptor neuropilin-2 in degenerate samples which were shown to contain nerves and blood vessels, compared to non-degenerate samples without nerves and blood vessels. Therefore data presented here suggests that semaphorin3C may have a role in promoting innervation and vascularisation during degeneration, which may go on to cause low back pain.

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