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Human annulus signaling cues for nerve outgrowth: In vitro studies
Author(s) -
Gruber Helen E.,
Hoelscher Gretchen L.,
Bullock Letitia,
Ingram Jane A.,
Norton H. James,
Hanley Edward N.
Publication year - 2016
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.23286
Subject(s) - in vitro , neuroscience , annulus (botany) , microbiology and biotechnology , biology , genetics , botany
The relationship between neurotrophins produced by human annulus cells, such as neurotrophin‐4 (NT4) and brain‐derived neurotrophic factor (BDNF) which function in neurite survival and outgrowth, and nerve ingrowth into the disc remains poorly understood. In this work, we tested F11 neurite growth during exposure to control media, media with added nerve growth factor (NGF), conditioned media (CM) harvested from previous human annulus culture, or co‐culture with annulus cells. Co‐culture of F11 cells with annulus cells significantly increased media levels of amphiregulin, BDNF, glial‐derived neurotrophic factor, and vascular endothelial growth factor compared to levels from in culture of F11 cells alone ( p ≤ 0.04). Cell‐based assays of neurite growth revealed that BDNF levels present in CM bore a significant ( p = 0.01) positive relationship to neurite length and accounted for 38.5% of the change in neurite length. NT4 levels produced during co‐culture with annulus cells bore a significant ( p = 0.04) positive relationship to neurite length and accounted for 40.9% of the change in length. Statement of clinical significance: In vitro findings point to a potential role of annulus cells related to nerve ingrowth in vivo, and may have relevance in the outer annulus (where cell numbers are high) or in regions where nerves penetrate into annular tears or fissures. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1456–1465, 2016.