| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Louis-Charles Simard Research Center, Centre Hospitalier de l’Université de Montréal (CHUM) Campus Notre-Dame and Department of Medicine, University of Montreal, Montreal, Quebec, Canada
Cytokines and growth factors regulate physiologic and pathologic turn-over of cartilage extracellular matrix (ECM) by altering the balance between tissue inhibitors of metalloproteinases (TIMPs) and matrix metalloproteinases (MMPs). Oncostatin M (OSM) is a cytokine of the IL-6 family whose levels are increased in the serum and synovial fluids of patients with rheumatoid arthritis. We examined responsiveness of the TIMP-3 gene to OSM in articular chondrocytes and studied the regulatory and signaling mechanisms of this response. OSM induced TIMP-3 mRNA and protein expression in a dose- and time-dependent fashion. Concomitantly, stromelysin-1 and collagenase-1 RNA and activities were also induced. A cartilage matrix growth factor, TGF-ß, induced TIMP-3, but combined OSM and TGF-ß did not further increase the extent of induction, suggesting a lack of synergy between the two. OSM induction of TIMP-3 gene expression was dependent upon de novo protein synthesis and transcription. RNA decay time-courses suggested that the OSM-mediated increase of TIMP-3 RNA was not due to enhanced message stability and, along with inhibition by actinomycin-D, suggested a transcriptional control. The antiinflammatory glucocorticoid, dexamethasone, down-regulated this augmentation. Investigation of the signaling mechanisms revealed that protein tyrosine kinase inhibitors genistein and herbimycin A, as well as the specific mitogen-activated protein kinase (MAPK) kinase inhibitor PD98059, suppressed OSM-induced TIMP-3 message expression, suggesting the involvement of tyrosine kinases and mitogen-activated protein kinase cascades in the signaling of OSM leading to TIMP-3 RNA enhancement. Thus OSM can potentially alter the cartilage matrix metabolism by regulating genes like TIMP-3 and matrix metalloproteinases.
This article has been cited by other articles:
|
|
 |
|
  C. Hintzen, C. Evers, B. E. Lippok, R. Volkmer, P. C. Heinrich, S. Radtke, and H. M. Hermanns Box 2 Region of the Oncostatin M Receptor Determines Specificity for Recruitment of Janus Kinases and STAT5 Activation J. Biol. Chem., July 11, 2008; 283(28): 19465 - 19477. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Cohen, S. Marchand-Adam, V. Lecon-Malas, J. Marchal-Somme, A. Boutten, G. Durand, B. Crestani, and M. Dehoux HGF synthesis in human lung fibroblasts is regulated by oncostatin M Am J Physiol Lung Cell Mol Physiol, June 1, 2006; 290(6): L1097 - L1103. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Somasundaram, M. Ruehl, B. Schaefer, M. Schmid, R. Ackermann, E. O. Riecken, M. Zeitz, and D. Schuppan Interstitial Collagens I, III, and VI Sequester and Modulate the Multifunctional Cytokine Oncostatin M J. Biol. Chem., January 25, 2002; 277(5): 3242 - 3246. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Q. Li, F. Dehnade, and M. Zafarullah Oncostatin M-Induced Matrix Metalloproteinase and Tissue Inhibitor of Metalloproteinase-3 Genes Expression in Chondrocytes Requires Janus Kinase/STAT Signaling Pathway J. Immunol., March 1, 2001; 166(5): 3491 - 3498. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kashiwagi, M. Tortorella, H. Nagase, and K. Brew TIMP-3 Is a Potent Inhibitor of Aggrecanase 1 (ADAM-TS4) and Aggrecanase 2 (ADAM-TS5) J. Biol. Chem., April 13, 2001; 276(16): 12501 - 12504. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. M. Hermanns, S. Radtke, F. Schaper, P. C. Heinrich, and I. Behrmann Non-redundant Signal Transduction of Interleukin-6-type Cytokines. THE ADAPTER PROTEIN Shc IS SPECIFICALLY RECRUITED TO THE ONCOSTATIN M RECEPTOR J. Biol. Chem., December 22, 2000; 275(52): 40742 - 40748. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
