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A Role for Soluble IL-6 Receptor in Osteoarthritis

Department of Medicine, Division of Rheumatic Diseases, Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA
Department of Medicine, University Hospitals Cleveland Medical Center, Foley Medical Building, 2061 Cornell Road, Room 207, Cleveland, OH 44106-5076, USA
Author to whom correspondence should be addressed.
J. Funct. Morphol. Kinesiol. 2017, 2(3), 27;
Received: 30 May 2017 / Revised: 4 July 2017 / Accepted: 25 July 2017 / Published: 2 August 2017
(This article belongs to the Special Issue Articular Cells and Tissues in Health and Osteoarthritis)
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Interleukin-6 (IL-6) is one of several pro-inflammatory cytokines present at elevated levels in the synovial fluid of individuals with confirmed clinical diagnosis of rheumatoid arthritis (RA) and osteoarthritis (OA). The mechanism of action of IL-6 was shown to involve its capacity to interact with a membrane-bound IL-6 receptor (mIL-6Rα), also known as the “classical” IL-6 pathway, or through its interaction with a soluble IL-6 receptor (sIL-6R) termed the “trans-signaling” pathway. Activation of downstream signaling is transduced via these IL-6 receptors and principally involves the Janus Kinase/Signal Transduction and Activators of Transcription (JAK/STAT) signaling pathway that is further regulated by glycoprotein-130 (gp130) interacting with the IL-6/mIL-6R complex. Phosphorylation of STAT proteins via JAK activation facilitates STAT proteins to act as transcription factors in inflammation. However, the biological function(s) of the sIL-6R in human chondrocytes requires further elucidation, although we previously showed that exogenous sIL-6R significantly suppressed the synthesis of neutrophil gelatinase-associated lipocalin (NGAL) in the immortalized line of human chondrocytes, C28/I2. NGAL was shown to regulate the activity of matrix metalloproteinase-9 (MMP-9), whose activity is crucial in OA for the destruction of articular cartilage. The “shedding” of sIL-6R from the plasma membrane is carried out by a family of enzymes known as A Distintegrin and Metalloproteinase (ADAM), which are also elevated in OA. In this paper, we have systematically reviewed the role played by IL-6 in OA. We have proposed that sIL-6R may be an important target for future drug development in OA by ameliorating cartilage extracellular protein degradation. View Full-Text
Keywords: a disintegrin and metalloproteinase; cytokines; inflammation; interleukin-6; interleukin-6 receptor; osteoarthritis; signal transduction a disintegrin and metalloproteinase; cytokines; inflammation; interleukin-6; interleukin-6 receptor; osteoarthritis; signal transduction

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Akeson, G.; Malemud, C.J. A Role for Soluble IL-6 Receptor in Osteoarthritis. J. Funct. Morphol. Kinesiol. 2017, 2, 27.

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J. Funct. Morphol. Kinesiol. EISSN 2411-5142 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
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