Annulus fibrosus cells interact with neuron-like cells to modulate production of growth factors and cytokines in symptomatic disc degeneration

Hong Joo Moon, Joo-Han Kim, Hack Sun Lee, Silky Chotai, James D. Kang, Jung Keun Suh, Youn-Kwan Park

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24 Citations (Scopus)


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 languageEnglish
Pages (from-to)2-9
Number of pages8
Issue number1
Publication statusPublished - 2012 Jan 1



  • AF cells
  • cytokines
  • growth factors
  • neovascularization
  • nerve ingrowth
  • SH-SY5Y cell line

ASJC Scopus subject areas

  • Clinical Neurology
  • Orthopedics and Sports Medicine

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