Enhanced SOCS3 in osteoarthiritis may limit both proliferation and inflammation

Gui, Tong; He, Bingshu; Gan, Qing-Fen; Yang, Changyi

doi:10.1080/10520295.2017.1278792

Cited by 15 publications

(9 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The nuclear factor-kappa B (NF-κB) transcription factor plays a central role in the pathogenesis of osteoarthritis [88]. It is triggered by proinflammatory cytokines and ECM degradation products [89].…”

Section: The Role Of Signaling Pathways and Other Inflammatory Componmentioning

confidence: 99%

The Role of Inflammation in the Pathogenesis of Osteoarthritis

Chow

Chin

2020

Mediators of Inflammation

338

221

View full text Add to dashboard Cite

A joint is the point of connection between two bones in our body. Inflammation of the joint leads to several diseases, including osteoarthritis, which is the concern of this review. Osteoarthritis is a common chronic debilitating joint disease mainly affecting the elderly. Several studies showed that inflammation triggered by factors like biomechanical stress is involved in the development of osteoarthritis. This stimulates the release of early-stage inflammatory cytokines like interleukin-1 beta (IL-1β), which in turn induces the activation of signaling pathways, such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), phosphoinositide 3-kinase/protein kinase B (PI3K/AKT), and mitogen-activated protein kinase (MAPK). These events, in turn, generate more inflammatory molecules. Subsequently, collagenase like matrix metalloproteinases-13 (MMP-13) will degrade the extracellular matrix. As a result, anatomical and physiological functions of the joint are altered. This review is aimed at summarizing the previous studies highlighting the involvement of inflammation in the pathogenesis of osteoarthritis.

show abstract

Section: The Role Of Signaling Pathways and Other Inflammatory Componmentioning

confidence: 99%

The Role of Inflammation in the Pathogenesis of Osteoarthritis

Chow

Chin

2020

Mediators of Inflammation

338

221

View full text Add to dashboard Cite

show abstract

“…SOCS3 protein is commonly known to serve as a negative regulator of STAT3, which is the key physiological regulator in immune homeostasis and diseases pathogenesis [ 89 – 91 ]. SOCS3 has been shown to be induced by a wide variety of the cytokines and growth factors, such as IL-1β, 2, 4 and M-CSF [ 92 , 93 ]. Unlike its closest homologue, SOCS-3 molecules differ greatly in their mechanism of function of SOCS-1.…”

Section: Socs Proteins Family and Macrophage Polarizationmentioning

confidence: 99%

SOCS molecules: the growing players in macrophage polarization and function

et al. 2017

View full text Add to dashboard Cite

The concept of macrophage polarization is defined in terms of macrophage phenotypic heterogeneity and functional diversity. Cytokines signals are thought to be required for the polarization of macrophage populations toward different phenotypes at different stages in development, homeostasis and disease. The suppressors of cytokine signaling family of proteins contribute to the magnitude and duration of cytokines signaling, which ultimately control the subtle adjustment of the balance between divergent macrophage phenotypes. This review highlights the specific roles and mechanisms of various cytokines family and their negative regulators link to the macrophage polarization programs. Eventually, breakthrough in the identification of these molecules will provide the novel therapeutic approaches for a host of diseases by targeting macrophage phenotypic shift.

show abstract

“…A previous study determined the prominent role of SOCS-3 in herniated lumbar disc degeneration by inhibiting the JAK/STAT3 signaling pathway (14). SOCS-3 also exhibits anti-inflammatory and anti-proliferation effects in osteoarthritis by downregulating levels of nuclear factor-κB and cyclooxygenase 2 (15). Dai et al (32) demonstrated that the upregulation of SOCS-3 expression results in reduced TNF-α levels and the regulation of Kallikrein-binding protein.…”

Section: Discussionmentioning

confidence: 99%

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

2019

View full text Add to dashboard Cite

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.

show abstract

Enhanced SOCS3 in osteoarthiritis may limit both proliferation and inflammation

Cited by 15 publications

References 30 publications

The Role of Inflammation in the Pathogenesis of Osteoarthritis

The Role of Inflammation in the Pathogenesis of Osteoarthritis

SOCS molecules: the growing players in macrophage polarization and function

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

Contact Info

Product

Resources

About