Ann Orthop Musculoskelet Disord | Volume 1, Issue 3 | Research Article | Open Access
Helen E Gruber*, Brittany Jones, Emilio Marrero and Edward N Hanley
Department of Orthopedic Surgery, Carolinas Health Care System, USA
*Correspondance to: Helen E Gruber
Fulltext PDFThe relationship between neurotrophins, nerves and human disc cells is still incompletely understood. GDNF has high relevance to the disc not only because past work has shown that GDNF supports survival and extension of neurites, but also because human annulus cells co-cultured with nerve cells produce GDNF. In this IRB-approved research study immune histochemistry was carried out to localize GDNF in human disc tissue and the proportion of positive cells was determined. GDNF gene expression was analyzed for human annulus cells were exposed to IL-1ß or TNF-α, and human annulus cells co-cultured with F11 nerve cells. Exogenous rhGDNF was also added to cultured annulus cells to test for a mitogenic response. Immune histochemistry verified GDNF presence in most annulus cells; the percentage of positive cells decreased significantly with increasing disc grade. In vitro production of GDNF by 3D cultured annulus cells was shown, with a significant increase in expression following exposure to IL-1ß or TNF-α (p = 0.007 and 0.004, respectively), and following co-culture with F11 nerve cells (p = 0.04). Rh GDNF (10 or 100 ng/ ml) did not induce a mitogenic response. Novel findings presented here showed GDNF expression/ production by annulus cells, and significant increase in its expression following exposure to IL-1ß or TNF-α, or following co-culture with F11 nerve cells. Because of its influence on nerve survival and neurite branching, findings have relevance to nerve in growth and pain in the outer annulus (where cell numbers are high), and in regions where nerves penetrate the disc via annular tears.
Gruber HE, Jones B, Marrero E, Hanley EN. Glial Cell-Derived Neurotropic Factor: Constitutive Expression in the Human Disc and up Regulation in vitro by Proinflammatory Cytokines. Ann Orthop Musculoskelet Disord. 2018;1(3):1011.