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SOCS1 Regulates Apoptosis and Inflammation by Inhibiting IL-4 Signaling in IL-1β-Stimulated Human Osteoarthritic Chondrocytes.

Abstract
Recently, Suppressor of Cytokine Signaling 1 (SOCS1) was identified as a potential therapeutic target for osteoarthritis (OA) treatment. However, the mechanisms and signaling pathways of SOCS1 in the regulation of OA development are unclear. The purpose of the current study was to investigate whether interleukin- (IL-) 4 was involved in regulatory mechanism of SOCS1 in human osteoarthritic chondrocytes. First, IL-1β was used to stimulate human osteoarthritic chondrocytes isolated from the articular cartilage of OA patients undergoing total knee replacement. The protein and mRNA expression levels of SOCS1 were upregulated in IL-1β-stimulated human osteoarthritic chondrocytes compared with control cells. The knockdown of SOCS1 increased cell viability and inhibited cell apoptosis. It was also found that IL-4 expression was increased by SOCS1 silencing. Additionally, knockdown of IL-4 reduced cell viability and increased cell apoptosis of osteoarthritic chondrocytes transfected with SOCS1 siRNA. Moreover, the decreased expression of inflammatory factors induced by SOCS1 was enhanced by IL-4 knockdown. In conclusion, IL-4 signaling plays a crucial role in the regulatory functions of SOCS1 in apoptosis and inflammation in human osteoarthritic chondrocytes. These findings provide a potential therapeutic target for the clinical treatment of OA.
AuthorsQiang He, Caihong Sun, Wei Lei, Jianbing Ma
JournalBioMed research international (Biomed Res Int) Vol. 2017 Pg. 4601959 ( 2017) ISSN: 2314-6141 [Electronic] United States
PMID28373981 (Publication Type: Journal Article)
Chemical References
  • Interleukin-1beta
  • SOCS1 protein, human
  • Suppressor of Cytokine Signaling 1 Protein
  • Interleukin-4
Topics
  • Aged
  • Apoptosis (drug effects, genetics)
  • Cartilage, Articular (metabolism, pathology)
  • Cell Line
  • Cell Survival (drug effects)
  • Chondrocytes (metabolism, pathology)
  • Female
  • Gene Expression Regulation (genetics)
  • Gene Knockdown Techniques
  • Humans
  • Inflammation (genetics, pathology, therapy)
  • Interleukin-1beta (administration & dosage, metabolism)
  • Interleukin-4 (biosynthesis, genetics)
  • Male
  • Middle Aged
  • Osteoarthritis (genetics, pathology, therapy)
  • Signal Transduction (genetics)
  • Suppressor of Cytokine Signaling 1 Protein (biosynthesis, genetics)

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