PMID- 28306638
OWN - NLM
STAT- MEDLINE
DCOM- 20190605
LR  - 20210114
IS  - 1528-1159 (Electronic)
IS  - 0362-2436 (Linking)
VI  - 42
IP  - 20
DP  - 2017 Oct 15
TI  - Proinflammatory Cytokines IL-1beta and TNF-alpha Influence Human Annulus Cell Signaling 
      Cues for Neurite Growth: In Vitro Coculture Studies.
PG  - 1529-1537
LID - 10.1097/BRS.0000000000002155 [doi]
AB  - STUDY DESIGN: Institutional review board-approved research using human annulus 
      cells cocultured with F11 nerve cells. OBJECTIVE: To perform functional, kinetic 
      assays of neurite dynamics and media neurotrophin measurements to test whether 
      proinflammatory cytokines influence annulus cells' signaling cues for neurite 
      growth/repulsion. SUMMARY OF BACKGROUND DATA: Nerves grow in response to 
      signaling molecules called neurotrophins, which disc cells produce (e.g., 
      brain-derived neurotrophic factor [BDNF], glial cell line-derived neurotrophic 
      factor [GDNF], and neurotrophin 3 [NT3]) and which influence neuron survival, 
      differentiation, and migration. How proinflammatory cytokines influence disc 
      signaling cues for neurite growth/repulsion is poorly understood. METHODS: 
      Studies used our previous model of 4-day human annulus cell-F11 nerve cell 
      coculture to assess effects of added proinflammatory cytokines interleukin 1 beta 
      (IL-1beta; 10 pmol/L) or tumor necrosis factor alpha (TNF-alpha) (10 pmol/L). Annulus 
      cells were cultured from 6 Thompson grade I, 9 grade II, 8 grade III, 11 grade 
      IV, and 7 grade V discs. Neurite lengths were measured following control 
      conditions or with added IL-1beta or TNF-alpha, and conditioned media assayed with 
      RayBiotech Growth Factor Arrays. Standard statistical methods used analysis of 
      variance and Spearman correlation coefficient testing associations of neurite 
      length with neurotrophin levels. RESULTS: IL-1-beta or TNF-alpha significantly increased 
      neurite lengths (P < 0.001) and BDNF, NT3, and GDNF media levels (P </= 0.01) 
      versus controls. Significant positive correlations were present between media 
      neurotrophin levels for BDNF, NT3, and GDNF and neurite lengths under control 
      conditions, following addition of IL-1beta, and following addition of TNF-alpha. Novel 
      data showed production of the neurotrophin amphiregulin. CONCLUSION: In vitro 
      data supported the hypothesis that nerve-disc cell interactions may be influenced 
      by the heightened proinflammatory milieu present in degenerating discs, leading 
      to increased nerve migration. Data may have direct clinical 
      relevance/implications for nerve ingrowth and pain in the outer annulus (where 
      disc cell numbers are high), and in regions where nerves penetrate into the disc 
      via annular tears. LEVEL OF EVIDENCE: N/A.
FAU - Gruber, Helen E
AU  - Gruber HE
AD  - Department of Orthopedic Surgery, Carolinas HealthCare System, Charlotte, NC.
FAU - Jones, Brittany
AU  - Jones B
FAU - Marrero, Emilio
AU  - Marrero E
FAU - Hanley, Edward N Jr
AU  - Hanley EN Jr
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Spine (Phila Pa 1976)
JT  - Spine
JID - 7610646
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Interleukin-1beta)
RN  - 0 (NTF3 protein, human)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Neurotrophin 3)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Annulus Fibrosus/drug effects/*metabolism
MH  - Cells, Cultured
MH  - Child
MH  - Child, Preschool
MH  - Coculture Techniques
MH  - Cues
MH  - Cytokines/metabolism/pharmacology
MH  - Female
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - Inflammation Mediators/metabolism
MH  - Interleukin-1beta/metabolism/*pharmacology
MH  - Intervertebral Disc/drug effects/metabolism
MH  - Male
MH  - Middle Aged
MH  - Nerve Growth Factors/metabolism
MH  - Neurites/drug effects/*metabolism
MH  - Neurotrophin 3
MH  - Prospective Studies
MH  - Signal Transduction/drug effects/*physiology
MH  - Tumor Necrosis Factor-alpha/metabolism/*pharmacology
MH  - Young Adult
EDAT- 2017/03/18 06:00
MHDA- 2019/06/06 06:00
CRDT- 2017/03/18 06:00
PHST- 2017/03/18 06:00 [pubmed]
PHST- 2019/06/06 06:00 [medline]
PHST- 2017/03/18 06:00 [entrez]
AID - 00007632-201710150-00004 [pii]
AID - 10.1097/BRS.0000000000002155 [doi]
PST - ppublish
SO  - Spine (Phila Pa 1976). 2017 Oct 15;42(20):1529-1537. doi: 
      10.1097/BRS.0000000000002155.