ArticleArthritis and rheumatism2009
Interleukin-7 stimulates secretion of S100A4 by activating the JAK/STAT signaling pathway in human articular chondrocytes.
Article in Arthritis and rheumatism, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 72 citations in OpenAlex.
- Unicompartmental and bicompartmental knee osteoarthritis show different patterns of mononuclear cell infiltration and cytokine release in the affected joints.Clinical and experimental immunology · 2015Trial
- Exercise-myokine relationships in osteoarthritis.Journal of translational medicine · 2026Review
- Grass carp S100A10a/10b, two skin wound-induced genes, augment epithelial cell proliferation and migration in vitro.Fish physiology and biochemistry · 2026Article
- Article
- Transcriptional Analysis Reveals That the FHL1/JAK-STAT Pathway is Involved in Acute Cartilage Injury in Mice.Cartilage · 2025Article
- A transcriptomic atlas at bulk and single-cell levels identifies novel transcriptional and splicing regulators of ECM homeostasis in osteoarthritis.Frontiers in genetics · 2025Article
- Renoprotective effects of extracellular fibroblast specific protein 1 via nuclear factor erythroid 2-related factor-mediated antioxidant activity.Scientific reports · 2023Article
- The Potential Role of Cytokines in Diabetic Intervertebral Disc Degeneration.Aging and disease · 2022Article
- S100A4/TCF Complex Transcription Regulation Drives Epithelial-Mesenchymal Transition in Chronic Sinusitis Through Wnt/GSK-3β/β-Catenin Signaling.Frontiers in immunology · 2022Article
- Interleukin (IL)-7 Signaling in the Tumor Microenvironment.Advances in experimental medicine and biology · 2021Article
- Extracellular S100A4 as a key player in fibrotic diseases.Journal of cellular and molecular medicine · 2020Review
- S100A4 promotes inflammation but suppresses lipid accumulation via the STAT3 pathway in chronic ethanol-induced fatty liver.Journal of molecular medicine (Berlin, Germany) · 2019Article
- Inflammation in osteoarthritis: is it time to dampen the alarm(in) in this debilitating disease?Clinical and experimental immunology · 2019Review
- The role of BMP6 in the proliferation and differentiation of chicken cartilage cells.PloS one · 2019Article
- S100 proteins as therapeutic targets.Biophysical reviews · 2018Review
- TLR4 and RAGE conversely mediate pro-inflammatory S100A8/9-mediated inhibition of proliferation-linked signaling in myeloproliferative neoplasms.Cellular oncology (Dordrecht, Netherlands) · 2018Article
- "Do We Know Jack" About JAK? A Closer Look at JAK/STAT Signaling Pathway.Frontiers in oncology · 2018Review
- Inhibitory effect of JAK inhibitor on mechanical stress-induced protease expression by human articular chondrocytes.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2017Article
- Role of metastasis-induced protein S100A4 in human non-tumor pathophysiologies.Cell & bioscience · 2017Review
- S100A4 protects the myocardium against ischemic stress.Journal of molecular and cellular cardiology · 2016Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
objectiveS100A4 has been shown to be increased in osteoarthritic (OA) cartilage and to stimulate chondrocytes to produce matrix metalloproteinase 13 (MMP-13) through activation of the receptor for advanced glycation end products (RAGE). The aim of this study was to examine the mechanism of S100A4 secretion by chondrocytes.
methodsHuman articular chondrocytes isolated from ankle cartilage were stimulated with 10 ng/ml of interleukin-1beta (IL-1beta), IL-6, IL-7, or IL-8. Cells were pretreated with either a JAK-3 inhibitor, brefeldin A, or cycloheximide. Immunoblotting with phospho-specific antibodies was used to determine the activation of signaling proteins. Secretion of S100A4 was measured in conditioned media by immunoblotting, and MMP-13 was measured by enzyme-linked immunosorbent assay.
resultsChondrocyte secretion of S100A4 was observed after treatment with IL-6 or IL-8 but was much greater in cultures treated with equal amounts of IL-7 and was not observed after treatment with IL-1beta. IL-7 activated the JAK/STAT pathway, with increased phosphorylation of JAK-3 and STAT-3, leading to increased production of S100A4 and MMP-13. Overexpression of a dominant-negative RAGE construct inhibited the IL-7-mediated production of MMP-13. Pretreatment of chondrocytes with a JAK-3 inhibitor or with cycloheximide blocked the IL-7-mediated secretion of S100A4, but pretreatment with brefeldin A did not.
conclusionIL-7 stimulates chondrocyte secretion of S100A4 via activation of JAK/STAT signaling, and then S100A4 acts in an autocrine manner to stimulate MMP-13 production via RAGE. Since both IL-7 and S100A4 are up-regulated in OA cartilage and can stimulate MMP-13 production by chondrocytes, this signaling pathway could contribute to cartilage destruction during the development of OA.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.