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Expression of semaphorin 3A and its receptors in the human intervertebral disc: potential role in regulating neural ingrowth in the degenerate intervertebral disc.

Tolofari SK, Richardson SM, Freemont AJ, Hoyland JA - Arthritis Res. Ther. (2010)

Bottom Line: In degenerate samples, sema3A expression decreased significantly in this region, although cell clusters within the degenerate nucleus pulposus exhibited strong immunopositivity. mRNA for sema3A receptors was also identified in healthy and degenerate tissues.This study is the first to establish the expression of semaphorins and their receptors in the human IVD with a decrease seen in the degenerate painful IVD.Sema3A may therefore, amongst other roles, act as a barrier to neuronal ingrowth within the healthy disc.

View Article: PubMed Central - HTML - PubMed

Affiliation: Tissue Injury and Repair Group, School of Clinical and Laboratory Sciences, University of Manchester, Stopford Building, Oxford Road, Manchester, M13 9PT, UK. Sotonye.tolofari@student.manchester.ac.uk

ABSTRACT

Introduction: Intervertebral disc (IVD) degeneration is considered a major underlying factor in the pathogenesis of chronic low back pain. Although the healthy IVD is both avascular and aneural, during degeneration there is ingrowth of nociceptive nerve fibres and blood vessels into proximal regions of the IVD, which may contribute to the pain. The mechanisms underlying neural ingrowth are, however, not fully understood. Semaphorin 3A (sema3A) is an axonal guidance molecule with the ability to repel nerves seeking their synaptic target. This study aimed to identify whether members of the Class 3 semaphorins were expressed by chondrocyte-like cells of the IVD addressing the hypothesis that they may play a role in repelling axons surrounding the healthy disc, thus maintaining its aneural condition.

Methods: Human IVD samples were investigated using reverse transcription polymerase chain reaction (RT-PCR) to identify gene expression of sema3A, 3F and their receptors: neuropilins (1 and 2) and plexins (A1-4). Sema3A protein was also localised within sections of normal and degenerate human IVD and immunopositivity quantified. Serial sections were stained using PGP9.5 and CD31 to correlate semaphorin 3A expression with nerve and blood vessel ingrowth, respectively.

Results: Sema3A protein was expressed highly in the healthy disc, primarily localised to the outer annulus fibrosus. In degenerate samples, sema3A expression decreased significantly in this region, although cell clusters within the degenerate nucleus pulposus exhibited strong immunopositivity. mRNA for sema3A receptors was also identified in healthy and degenerate tissues. CD31 and PGP9.5 were expressed most highly in degenerate tissues correlating with low expression of sema3A.

Conclusions: This study is the first to establish the expression of semaphorins and their receptors in the human IVD with a decrease seen in the degenerate painful IVD. Sema3A may therefore, amongst other roles, act as a barrier to neuronal ingrowth within the healthy disc.

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Histogram illustrating the percentage of cells positive for sema3A per morphological region and stage of degeneration. Values are mean ± SEM. *P < 0.05.
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Figure 3: Histogram illustrating the percentage of cells positive for sema3A per morphological region and stage of degeneration. Values are mean ± SEM. *P < 0.05.

Mentions: Immunopositivity was localised primarily to cells within the AF with approximately 80% of cells demonstrating positivity for sema3A (Figure 3). A gradient of expression was observed more proximally in the disc as the cells of the IAF showed 40% positivity and the NP cells only showed 5% positivity. There were significant differences (P ≤ 0.01) in the number of cells demonstrating positivity for sema3A between all three morphological regions of the IVD (Figure 3).


Expression of semaphorin 3A and its receptors in the human intervertebral disc: potential role in regulating neural ingrowth in the degenerate intervertebral disc.

Tolofari SK, Richardson SM, Freemont AJ, Hoyland JA - Arthritis Res. Ther. (2010)

Histogram illustrating the percentage of cells positive for sema3A per morphological region and stage of degeneration. Values are mean ± SEM. *P < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2875625&req=5

Figure 3: Histogram illustrating the percentage of cells positive for sema3A per morphological region and stage of degeneration. Values are mean ± SEM. *P < 0.05.
Mentions: Immunopositivity was localised primarily to cells within the AF with approximately 80% of cells demonstrating positivity for sema3A (Figure 3). A gradient of expression was observed more proximally in the disc as the cells of the IAF showed 40% positivity and the NP cells only showed 5% positivity. There were significant differences (P ≤ 0.01) in the number of cells demonstrating positivity for sema3A between all three morphological regions of the IVD (Figure 3).

Bottom Line: In degenerate samples, sema3A expression decreased significantly in this region, although cell clusters within the degenerate nucleus pulposus exhibited strong immunopositivity. mRNA for sema3A receptors was also identified in healthy and degenerate tissues.This study is the first to establish the expression of semaphorins and their receptors in the human IVD with a decrease seen in the degenerate painful IVD.Sema3A may therefore, amongst other roles, act as a barrier to neuronal ingrowth within the healthy disc.

View Article: PubMed Central - HTML - PubMed

Affiliation: Tissue Injury and Repair Group, School of Clinical and Laboratory Sciences, University of Manchester, Stopford Building, Oxford Road, Manchester, M13 9PT, UK. Sotonye.tolofari@student.manchester.ac.uk

ABSTRACT

Introduction: Intervertebral disc (IVD) degeneration is considered a major underlying factor in the pathogenesis of chronic low back pain. Although the healthy IVD is both avascular and aneural, during degeneration there is ingrowth of nociceptive nerve fibres and blood vessels into proximal regions of the IVD, which may contribute to the pain. The mechanisms underlying neural ingrowth are, however, not fully understood. Semaphorin 3A (sema3A) is an axonal guidance molecule with the ability to repel nerves seeking their synaptic target. This study aimed to identify whether members of the Class 3 semaphorins were expressed by chondrocyte-like cells of the IVD addressing the hypothesis that they may play a role in repelling axons surrounding the healthy disc, thus maintaining its aneural condition.

Methods: Human IVD samples were investigated using reverse transcription polymerase chain reaction (RT-PCR) to identify gene expression of sema3A, 3F and their receptors: neuropilins (1 and 2) and plexins (A1-4). Sema3A protein was also localised within sections of normal and degenerate human IVD and immunopositivity quantified. Serial sections were stained using PGP9.5 and CD31 to correlate semaphorin 3A expression with nerve and blood vessel ingrowth, respectively.

Results: Sema3A protein was expressed highly in the healthy disc, primarily localised to the outer annulus fibrosus. In degenerate samples, sema3A expression decreased significantly in this region, although cell clusters within the degenerate nucleus pulposus exhibited strong immunopositivity. mRNA for sema3A receptors was also identified in healthy and degenerate tissues. CD31 and PGP9.5 were expressed most highly in degenerate tissues correlating with low expression of sema3A.

Conclusions: This study is the first to establish the expression of semaphorins and their receptors in the human IVD with a decrease seen in the degenerate painful IVD. Sema3A may therefore, amongst other roles, act as a barrier to neuronal ingrowth within the healthy disc.

Show MeSH
Related in: MedlinePlus