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

    Research output: Contribution to journalArticlepeer-review

    35 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
    • SH-SY5Y cell line
    • cytokines
    • growth factors
    • neovascularization
    • nerve ingrowth

    ASJC Scopus subject areas

    • Orthopedics and Sports Medicine
    • Clinical Neurology


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