Abstract
Study Design: We hypothesized that AF/neuron interactions during annular injury were involved in neovascularization and nerve ingrowth, the pathologic hallmarks of symptomatic disc degeneration. Objective: To identify growth factors and inflammatory cytokines related to AF/neuron interactions using in vitro model. Summary of Background Data: Discogenic pain is the chronic intractable pain initiated by tears in the outer annulus fibrosus (AF); this is a unique structure with free nerve endings at outer one-third, located beside dorsal root ganglia. The relationship between AF and neuron cells in annular injury has not been extensively investigated. Methods: Human AF cells were cocultured with a retinoic acid (RA)-treated SH-SY5Y human neuroblastoma cell line (neuron-like cells). Conditioned media from cells cultured alone or in coculture were assayed for growth factors and inflammatory cytokines using enzyme-linked immunosorbent assays. The responses of the neuron-like cells, the AF cells, and the cocultured group to IL-1β/TNF-α were compared using the same outcome measures. Results: RA-treated SH-SY5Y cells showed significant neurite outgrowth on the 7th day; this is a typical morphologic finding of neuron-like cells. Neuron-like cells produced vascular endothelial growth factor (VEGF) and IGF-1 under basal conditions and dose-dependently secreted small amounts of IL-8 in response to TNF-α. Coculturing enhanced the secretion of VEGF, TGF-β1, and β-NGF, and suppressed the production of IGF-1. VEGF in the coculture group and the AF cells was downregulated by IL-1β/TNF-α stimulation. IL-1β/TNF-α stimulation enhanced the production of large amounts of IL-6 and IL-8 from AF cells; IL-1β produced a greater response than TNF-α. The neuron-like cells did not produce detectable amounts of IL-6 or IL-8. Conclusion: These studies suggest that AF cells are involved in an inflammatory reaction and that the interactions between AF and neuron-like cells enhance the production of growth factors responsible for neovascularization and nerve ingrowth. AF injury has the potential to initiate neovascularization/nerve ingrowth and an inflammatory reaction through the interactions of AF and neural tissues.
| Original language | English |
|---|---|
| Pages (from-to) | 2-9 |
| Number of pages | 8 |
| Journal | Spine |
| Volume | 37 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2012 Jan 1 |
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Keywords
- AF cells
- cytokines
- growth factors
- neovascularization
- nerve ingrowth
- SH-SY5Y cell line
ASJC Scopus subject areas
- Clinical Neurology
- Orthopedics and Sports Medicine
Cite this
Annulus fibrosus cells interact with neuron-like cells to modulate production of growth factors and cytokines in symptomatic disc degeneration. / Moon, Hong Joo; Kim, Joo-Han; Lee, Hack Sun; Chotai, Silky; Kang, James D.; Suh, Jung Keun; Park, Youn-Kwan.
In: Spine, Vol. 37, No. 1, 01.01.2012, p. 2-9.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Annulus fibrosus cells interact with neuron-like cells to modulate production of growth factors and cytokines in symptomatic disc degeneration
AU - Moon, Hong Joo
AU - Kim, Joo-Han
AU - Lee, Hack Sun
AU - Chotai, Silky
AU - Kang, James D.
AU - Suh, Jung Keun
AU - Park, Youn-Kwan
PY - 2012/1/1
Y1 - 2012/1/1
N2 - Study Design: We hypothesized that AF/neuron interactions during annular injury were involved in neovascularization and nerve ingrowth, the pathologic hallmarks of symptomatic disc degeneration. Objective: To identify growth factors and inflammatory cytokines related to AF/neuron interactions using in vitro model. Summary of Background Data: Discogenic pain is the chronic intractable pain initiated by tears in the outer annulus fibrosus (AF); this is a unique structure with free nerve endings at outer one-third, located beside dorsal root ganglia. The relationship between AF and neuron cells in annular injury has not been extensively investigated. Methods: Human AF cells were cocultured with a retinoic acid (RA)-treated SH-SY5Y human neuroblastoma cell line (neuron-like cells). Conditioned media from cells cultured alone or in coculture were assayed for growth factors and inflammatory cytokines using enzyme-linked immunosorbent assays. The responses of the neuron-like cells, the AF cells, and the cocultured group to IL-1β/TNF-α were compared using the same outcome measures. Results: RA-treated SH-SY5Y cells showed significant neurite outgrowth on the 7th day; this is a typical morphologic finding of neuron-like cells. Neuron-like cells produced vascular endothelial growth factor (VEGF) and IGF-1 under basal conditions and dose-dependently secreted small amounts of IL-8 in response to TNF-α. Coculturing enhanced the secretion of VEGF, TGF-β1, and β-NGF, and suppressed the production of IGF-1. VEGF in the coculture group and the AF cells was downregulated by IL-1β/TNF-α stimulation. IL-1β/TNF-α stimulation enhanced the production of large amounts of IL-6 and IL-8 from AF cells; IL-1β produced a greater response than TNF-α. The neuron-like cells did not produce detectable amounts of IL-6 or IL-8. Conclusion: These studies suggest that AF cells are involved in an inflammatory reaction and that the interactions between AF and neuron-like cells enhance the production of growth factors responsible for neovascularization and nerve ingrowth. AF injury has the potential to initiate neovascularization/nerve ingrowth and an inflammatory reaction through the interactions of AF and neural tissues.
AB - Study Design: We hypothesized that AF/neuron interactions during annular injury were involved in neovascularization and nerve ingrowth, the pathologic hallmarks of symptomatic disc degeneration. Objective: To identify growth factors and inflammatory cytokines related to AF/neuron interactions using in vitro model. Summary of Background Data: Discogenic pain is the chronic intractable pain initiated by tears in the outer annulus fibrosus (AF); this is a unique structure with free nerve endings at outer one-third, located beside dorsal root ganglia. The relationship between AF and neuron cells in annular injury has not been extensively investigated. Methods: Human AF cells were cocultured with a retinoic acid (RA)-treated SH-SY5Y human neuroblastoma cell line (neuron-like cells). Conditioned media from cells cultured alone or in coculture were assayed for growth factors and inflammatory cytokines using enzyme-linked immunosorbent assays. The responses of the neuron-like cells, the AF cells, and the cocultured group to IL-1β/TNF-α were compared using the same outcome measures. Results: RA-treated SH-SY5Y cells showed significant neurite outgrowth on the 7th day; this is a typical morphologic finding of neuron-like cells. Neuron-like cells produced vascular endothelial growth factor (VEGF) and IGF-1 under basal conditions and dose-dependently secreted small amounts of IL-8 in response to TNF-α. Coculturing enhanced the secretion of VEGF, TGF-β1, and β-NGF, and suppressed the production of IGF-1. VEGF in the coculture group and the AF cells was downregulated by IL-1β/TNF-α stimulation. IL-1β/TNF-α stimulation enhanced the production of large amounts of IL-6 and IL-8 from AF cells; IL-1β produced a greater response than TNF-α. The neuron-like cells did not produce detectable amounts of IL-6 or IL-8. Conclusion: These studies suggest that AF cells are involved in an inflammatory reaction and that the interactions between AF and neuron-like cells enhance the production of growth factors responsible for neovascularization and nerve ingrowth. AF injury has the potential to initiate neovascularization/nerve ingrowth and an inflammatory reaction through the interactions of AF and neural tissues.
KW - AF cells
KW - cytokines
KW - growth factors
KW - neovascularization
KW - nerve ingrowth
KW - SH-SY5Y cell line
UR - http://www.scopus.com/inward/record.url?scp=84655176540&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84655176540&partnerID=8YFLogxK
U2 - 10.1097/BRS.0b013e31820cd2d8
DO - 10.1097/BRS.0b013e31820cd2d8
M3 - Article
C2 - 21386768
AN - SCOPUS:84655176540
VL - 37
SP - 2
EP - 9
JO - Spine
JF - Spine
SN - 0362-2436
IS - 1
ER -