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TNF‐α suppresses SHOX2 expression via NF‐κB signaling pathway and promotes intervertebral disc degeneration and related pain in a rat model
Author(s) -
Ye Fubiao,
Xu Yang,
Lin Feiyue,
Zheng Zhaomin
Publication year - 2021
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.24832
Subject(s) - western blot , tumor necrosis factor alpha , mapk/erk pathway , in vivo , immunohistochemistry , blot , signal transduction , nf κb , intervertebral disc , p38 mitogen activated protein kinases , medicine , microbiology and biotechnology , biology , anatomy , biochemistry , gene , genetics
This study was conducted to verify the relative expression patterns of SHOX2 and its regulation by tumor necrosis factor alpha (TNF‐α) during the development of intervertebral disc degeneration (IVDD). A rat disc‐degeneration model was subjected to disc puncture (DP) and intradiscal injections with TNF‐α to determine the roles of TNF‐α and SHOX2 expression in IVDD in vivo. TNF‐α and SHOX2 expression patterns in different degenerative rat nucleus pulposus (NP) tissues were measured by immunohistochemistry (IHC). The effects of TNF‐α on IVDD were determined by magnetic resonance imaging (MRI) and pain development of wet‐dog shakes (WDS) were blinded assessment by pain‐behavior testing, respectively. Changes in TNF‐α on SHOX2 expression were measured by Western blot analysis and real‐time reverse transcription polymerase chain reaction (RT‐PCR). The roles of nuclear factor‐κB (NF‐κB) and mitogen‐activated protein kinase (MAPK) in TNF‐α‐mediated SHOX2 activation were studied using viral transfection, Western blot analysis, and real‐time RT‐PCR. In vivo, TNF‐α accelerated the process of IVDD and suppressed SHOX2 expression; compared to the DP group, WDS was significantly increased in TNF‐α intradiscal injection group at 2 to 6 weeks after puncture ( P < .05); In NP cells, TNF‐α negatively affected the IVDD‐associated SHOX2 suppression. While TNF‐α promotes IVDD through activation of both MAPK and NF‐κB signaling, it seemed that only NF‐κB signaling controlled the TNF‐α‐mediated SHOX2 suppression that is associated with IVDD. The results of this study indicated that TNF‐α inhibits SHOX2 expression and has promoted effects on IVDD in the rat model, and these effects might be associated with through NF‐κB signaling pathway and promotes IVDD and related pain in a rat model.