CCAAT/enhancer binding protein β regulates the expression of tumor necrosis factor-α in the nucleus pulposus cells.
Tumor necrosis factor alpha (TNF-α) is important in the process of intervertebral disc (IVD) degeneration because of its ability to regulate other inflammatory mediators in autocrine and paracrine fashions. The mechanism responsible for the cell type-specific regulation of TNF-α is not well known. CCAAT/enhancer binding protein β (C/EBP β) is one of the transcriptional factors that is implicated in TNF-α expression. However, it is not known whether cross talk occurs between C/EBP β and the TNF-α pathway in IVD cells. The expression and effect of the C/EBP β mRNA and protein in rat IVD cells was assessed using real-time reverse transcription polymerase chain reaction, immunohistochemical, and immunofluorescence analyses. We present data that show that the C/EBP β mRNA and protein were expressed in rat and human IVDs in vivo. We also found that the expression of TNF-α is regulated by the transcription factor C/EBP β in rat NP cells. The TNF-α promoter was suppressed completely in the presence of the ERK inhibitor PD98059 and the p38 mitogen-activated protein kinase (MAPK) inhibitor SB202190, but not in the presence of the JNK inhibitor SP600125. In addition, gain and loss of function analyses showed that the expression of TNF-α was regulated by C/EBP β through the MAPK pathways. These findings showed that C/EBP β acts as a potent pro-inflammatory mediator by inducing the TNF-α gene at the transcription and protein levels via the ERK1/2 and p38 pathways in rat NP cells. Our findings may open a new avenue toward the understanding of the cellular and molecular mechanisms of IVD cells. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:865-875, 2016.
Department of Orthopaedic Surgery, Surgical Science, Tokai University School of Medicine, 143 Shimokasuya, Isehara, 259-1193, Kanagawa, Japan.|Research Center for Regenerative Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, 259-1193, Kanagawa, Japan.
Akihiko
A
Hiyama
Department of Orthopaedic Surgery, Surgical Science, Tokai University School of Medicine, 143 Shimokasuya, Isehara, 259-1193, Kanagawa, Japan.|Research Center for Regenerative Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, 259-1193, Kanagawa, Japan.
Shunsuke
S
Hiraishi
Department of Orthopaedic Surgery, Surgical Science, Tokai University School of Medicine, 143 Shimokasuya, Isehara, 259-1193, Kanagawa, Japan.|Research Center for Regenerative Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, 259-1193, Kanagawa, Japan.
Daisuke
D
Sakai
Department of Orthopaedic Surgery, Surgical Science, Tokai University School of Medicine, 143 Shimokasuya, Isehara, 259-1193, Kanagawa, Japan.|Research Center for Regenerative Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, 259-1193, Kanagawa, Japan.
Joji
J
Mochida
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D020935:MAP Kinase Signaling System; D008875:Middle Aged; D000070614:Nucleus Pulposus / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D055815:Young Adult
D022782:CCAAT-Enhancer-Binding Protein-beta; D014409:Tumor Necrosis Factor-alpha
CCAAT/enhancer binding; MAPK signaling; TNF-α; cells; intervertebral disc cells; nucleus pulposus