Class 3 semaphorins expression and association with innervation and angiogenesis within the degenerate human intervertebral disc.
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.
Sheffield Hallam University, Sheffield, South Yorkshire, United Kingdom.
Abbie L A
AL
Binch
Sheffield Teaching Hospitals, Sheffield, South Yorkshire, United Kingdom.
Ashley A
AA
Cole
Sheffield Teaching Hospitals, Sheffield, South Yorkshire, United Kingdom.
Lee M
LM
Breakwell
Sheffield Teaching Hospitals, Sheffield, South Yorkshire, United Kingdom.
Anthony L R
AL
Michael
Sheffield Teaching Hospitals, Sheffield, South Yorkshire, United Kingdom.
Neil
N
Chiverton
Universitair Medisch Centrum, Orthopaedics Department, Utrecht, Netherlands.
Laura B
LB
Creemers
Sheffield Hallam University, Sheffield, South Yorkshire, United Kingdom.
Alison K
AK
Cross
Sheffield Hallam University, Sheffield, South Yorkshire, United Kingdom.
Christine L
CL
Le Maitre
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D007403:Intervertebral Disc / Q000098:blood supply / Q000294:innervation / Q000378:metabolism*; D055959:Intervertebral Disc Degeneration / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D039943:Neuropilin-2 / Q000235:genetics* / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D039961:Semaphorins / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D055815:Young Adult
D016207:Cytokines; D039943:Neuropilin-2; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D039961:Semaphorins
Pathology Section; angiogenesis; cytokines; innervation; intervertebral disc; semaphorins