Upregulation of suppressor of cytokine signaling 3 ameliorates spinal degenerative disease in adolescents by mediating leptin and tumor necrosis factor‑α levels

Tang,Xiao‑Ming; Dai,Jian; Sun,Hai‑Lang

doi:10.3892/etm.2019.7786

Upregulation of suppressor of cytokine signaling 3 ameliorates spinal degenerative disease in adolescents by mediating leptin and tumor necrosis factor‑α levels

Authors:
- Xiao‑Ming Tang
- Jian Dai
- Hai‑Lang Sun
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Affiliations: Department of Orthopedics, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China
Published online on: July 17, 2019 https://doi.org/10.3892/etm.2019.7786
Pages: 2231-2237

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Abstract

Spinal degenerative changes may occur following the rapid growth observed in adolescents, causing a reduced quality of life. The suppressor of cytokine signaling (SOCS) is involved in various degenerative diseases. The current study recruited adolescents with spinal degenerative disease (SDD) to identify the effect of SOCS‑3 on leptin and tumor necrosis factor‑α (TNF‑α) levels in this disorder. From January 2010 to January 2016, 120 adolescents (aged 14 to 25) were enrolled in the current study, with 68 diagnosed with SDD and the remaining 52 treated as controls. Nucleus pulposus cells (NPCs) were extracted and cultured in vitro. TNF‑α levels in NPCs were determined using flow cytometry. Degenerative NPCs were then transfected with pCR3.1‑SOCS‑3 and ELISA was performed to determined TNF‑α and leptin levels. RT‑qPCR was performed to measure the mRNA level of SOCS‑3 and leptin in NPCs and western blotting was utilized to detect the protein level of leptin and the extent of leptin receptor phosphorylation. The results revealed that TNF‑α levels in degenerative NPCs were higher than those in normal NPCs. The overexpression of SOCS‑3 reduced levels of TNF‑α and leptin in degenerative NPCs. In addition, the upregulation of leptin increased SOCS‑3 levels in a concentration‑dependent manner. Furthermore, the expression of the leptin receptor and phosphorylated leptin receptor gradually decreased with increasing leptin concentrations and the level of phosphorylated leptin receptor negatively correlated with SOCS‑3 expression. The inductive effect of leptin on the level of SOCS‑3 and the inhibitory effect of SOCS‑3 on the activity of leptin were identified. The current study demonstrated that SOCS‑3 reduces leptin and TNF‑α levels in degenerative NPCs from adolescents, indicating its potential role in the development of novel SDD therapies.

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