A novel role for suppressor of cytokine signaling 3 in cartilage destruction via induction of chondrocyte desensitization toward insulin-like growth factor

Arthritis and Rheumatism
R L SmeetsFons A J van de Loo

Abstract

An important mechanism contributing to cartilage destruction in arthritis is chondrocyte desensitization toward its main anabolic factor, insulin-like growth factor 1 (IGF-1). In this study, we sought to determine the role of suppressor of cytokine signaling 3 (SOCS-3) in the induction of IGF-1 desensitization of murine chondrocytes. Chondrocyte responsiveness to IGF-1 was assessed by 35S-sulfate incorporation into proteoglycans (PGs), via aggrecan messenger RNA expression, using quantitative real-time polymerase chain reaction or insulin receptor substrate 1 (IRS-1) tyrosine phosphorylation (Western blot analysis). IGF-1 desensitization of patellar chondrocytes was studied in zymosan-induced arthritis. IGF-1 desensitization was induced in patellar cartilage explants or the H4 chondrocyte cell line, exposed to interleukin-1alpha (IL-1alpha). SOCS-3 protein expression was assessed by immunohistochemistry or by Western blot analysis of protein extracts. The role of SOCS-3 in IGF-1 signaling was elucidated by adenoviral overexpression. Exposure of murine articular cartilage to IL-1 caused a significant decrease in IGF-1-induced PG synthesis. This effect also occurred in inducible nitric oxide synthase-knockout mice, revealing the ...Continue Reading

References

Jan 1, 1989·Arthritis and Rheumatism·J SchalkwijkL B van de Putte
Jan 1, 1996·Methods in Enzymology·C H EvansM Stefanović-Racić
Jul 15, 1998·Arthritis and Rheumatism·R M ClancyS B Abramson
Mar 3, 1999·Proceedings of the National Academy of Sciences of the United States of America·J G ZhangM Baca
May 24, 2000·The Journal of Biological Chemistry·B EmanuelliE Van Obberghen
Sep 26, 2000·American Journal of Physiology. Cell Physiology·R K StuderC H Evans
Nov 22, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·L A JoostenW B van Den Berg
Jul 3, 2002·Nature Reviews. Immunology·Warren S Alexander
Dec 5, 2002·Osteoarthritis and Cartilage·H M van BeuningenW B van den Berg
Mar 21, 2003·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Lykke Larsen, Carsten Röpke
Aug 16, 2003·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·R K StuderH Georgescu
Dec 3, 2003·Trends in Immunology·Minoru Fujimoto, Tetsuji Naka
Feb 15, 2005·Annals of the Rheumatic Diseases·E ManeiroF J Blanco

❮ Previous
Next ❯

Citations

Nov 16, 2007·Arthritis Research & Therapy·Miguel Otero, Mary B Goldring
Jun 3, 2008·Arthritis Research & Therapy·Morten A KarsdalBodil C Sondergaard
Jun 13, 2009·Arthritis Research & Therapy·Mary B Goldring, Kenneth B Marcu
Jul 8, 2011·PM & R : the Journal of Injury, Function, and Rehabilitation·Michael B Mueller, Rocky S Tuan
Sep 12, 2015·Arthritis & Rheumatology·Martijn H van den BoschPeter L van Lent
May 6, 2008·Best Practice & Research. Clinical Rheumatology·Johanne Martel-PelletierPeter J Roughley
Aug 19, 2015·International Journal of Pediatric Otorhinolaryngology·Gangqiang Wei
Mar 18, 2011·Bioelectromagnetics·Alessia OngaroMonica De Mattei
May 12, 2012·Arthritis and Rheumatism·Fons A J van de LooWim B van den Berg
Dec 2, 2009·Arthritis and Rheumatism·Bernard VandoorenDominique Baeten
Sep 19, 2006·Best Practice & Research. Clinical Rheumatology·Mary B Goldring
Apr 22, 2016·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·Sen WangXiong Guo
Mar 16, 2017·Biotechnic & Histochemistry : Official Publication of the Biological Stain Commission·T GuiC Yang
Sep 16, 2017·Connective Tissue Research·Tong LiXiaoxia Zuo
Jul 22, 2020·Rheumatology·Renske WiegertjesEsmeralda N Blaney Davidson
Oct 9, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Cheng-Rong YuCharles E Egwuagu

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.