title: Human annulus signaling cues for nerve outgrowth: In vitro studies.
abstract: 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.
authors.affiliation: Department of Orthopaedic Surgery, Carolinas Medical Center, PO Box 32861, Charlotte, North Carolina, 28232.
authors.forename: Helen E
authors.initials: HE
authors.lastname: Gruber
authors.affiliation: Department of Orthopaedic Surgery, Carolinas Medical Center, PO Box 32861, Charlotte, North Carolina, 28232.
authors.forename: Gretchen L
authors.initials: GL
authors.lastname: Hoelscher
authors.affiliation: Department of Orthopaedic Surgery, Carolinas Medical Center, PO Box 32861, Charlotte, North Carolina, 28232.
authors.forename: Letitia
authors.initials: L
authors.lastname: Bullock
authors.affiliation: Department of Orthopaedic Surgery, Carolinas Medical Center, PO Box 32861, Charlotte, North Carolina, 28232.
authors.forename: Jane A
authors.initials: JA
authors.lastname: Ingram
authors.affiliation: Dickson Advanced Analytics, Carolinas Medical Center, PO Box 32861, Charlotte, North Carolina.
authors.forename: H James
authors.initials: HJ
authors.lastname: Norton
authors.affiliation: Department of Orthopaedic Surgery, Carolinas Medical Center, PO Box 32861, Charlotte, North Carolina, 28232.
authors.forename: Edward N
authors.initials: EN
authors.lastname: Hanley
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000070616:Annulus Fibrosus / Q000294:innervation* / Q000378:metabolism; D018920:Coculture Techniques; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D017116:Low Back Pain / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000378:metabolism*; D016501:Neurites / Q000502:physiology*; D055815:Young Adult
chemical_list: D009414:Nerve Growth Factors
keywords: BDNF; disc pain; nerve growth; neurotrophin 3; neurotrophin 4