title: 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-1βwas 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.
authors.affiliation: Department of Orthopaedic Surgery, Honghui Hospital, Xi'an Jiaotong University, No. 555 East Youyi Road, Xi'an, Shaanxi 710054, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: He
authors.affiliation: Department of Informatics, 451 Hospital of PLA, No. 169 East Youyi Road, Xi'an, Shaanxi 710054, China.
authors.forename: Caihong
authors.initials: C
authors.lastname: Sun
authors.affiliation: Institute of Orthopaedics, Xijing Hospital, Fourth Military Medical University, No. 169 West Changle Road, Xi'an, Shaanxi 710032, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lei
authors.affiliation: Department of Orthopaedic Surgery, Honghui Hospital, Xi'an Jiaotong University, No. 555 East Youyi Road, Xi'an, Shaanxi 710054, China.
authors.forename: Jianbing
authors.identifier: 0000-0001-8065-0262
authors.initials: J
authors.lastname: Ma
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D055785:Gene Knockdown Techniques; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D053583:Interleukin-1beta / Q000008:administration & dosage / Q000378:metabolism; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D015398:Signal Transduction / Q000235:genetics; D000071222:Suppressor of Cytokine Signaling 1 Protein / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D053583:Interleukin-1beta; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D015847:Interleukin-4