| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
/CXCL1 Induce Chondrocyte Hypertrophic Differentiation 1
Veterans Affairs Medical Center, University of California at San Diego, La Jolla, CA
Foci of chondrocyte hypertrophy that commonly develop in osteoarthritic (OA) cartilage can promote dysregulated matrix repair and pathologic calcification in OA. The closely related chemokines IL-8/CXCL8 and growth-related oncogene 
(GRO)/CXCL1 and their receptors are up-regulated in OA cartilage chondrocytes. Because these chemokines regulate leukocyte activation through p38 mitogen-activated protein kinase signaling, a pathway implicated in chondrocyte hypertrophic differentiation, we tested whether IL-8 and GRO promote chondrocyte hypertrophy. We observed that normal human and bovine primary articular chondrocytes expressed both IL-8Rs (CXCR1, CXCR2). IL-8 and the selective CXCR2 ligand GRO (10 ng/ml) induced tissue inhibitor of metalloproteinase-3 expression, markers of hypertrophy (type X collagen and MMP-13 expression, alkaline phosphatase activity), as well as matrix calcification. IL-8 and the selective CXCR2 ligand GRO also induced increased transamidation activity of chondrocyte transglutaminases (TGs), enzymes up-regulated in chondrocyte hypertrophy that have the potential to modulate differentiation and calcification. Under these conditions, p38 mitogen-activated protein kinase pathway signaling mediated induction of both type X collagen and TG activity. Studies using mouse knee chondrocytes lacking one of the two known articular chondrocyte-expressed TG isoenzymes (TG2) demonstrated that TG2 was essential for murine GRO homologue KC-induced TG activity and critically mediated induction by KC of type X collagen, matrix metalloproteinase-13, alkaline phosphatase, and calcification. In conclusion, IL-8 and GRO induce articular chondrocyte hypertrophy and calcification through p38 and TG2. Our results suggest a novel linkage between inflammation and altered differentiation of articular chondrocytes. Furthermore, CXCR2 and TG2 may be sites for intervention in the pathogenesis of OA.
This article has been cited by other articles:
|
|
 |
|
  K. A. Johnson, D. M. Rose, and R. A. Terkeltaub Factor XIIIA mobilizes transglutaminase 2 to induce chondrocyte hypertrophic differentiation J. Cell Sci., July 1, 2008; 121(13): 2256 - 2264. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Cecil and R. Terkeltaub Transamidation by Transglutaminase 2 Transforms S100A11 Calgranulin into a Procatabolic Cytokine for Chondrocytes J. Immunol., June 15, 2008; 180(12): 8378 - 8385. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Johnson, M. Polewski, and R. A. Terkeltaub Transglutaminase 2 Is Central to Induction of the Arterial Calcification Program by Smooth Muscle Cells Circ. Res., March 14, 2008; 102(5): 529 - 537. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. B. Levashova, N. Sharma, O. A. Timofeeva, J. S. Dome, and A. O. Perantoni ELR+-CXC Chemokines and Their Receptors in Early Metanephric Development J. Am. Soc. Nephrol., August 1, 2007; 18(8): 2359 - 2370. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.A. Boisvert, D.M. Rose, A. Boullier, O. Quehenberger, A. Sydlaske, K.A Johnson, L.K. Curtiss, and R. Terkeltaub Leukocyte Transglutaminase 2 Expression Limits Atherosclerotic Lesion Size Arterioscler. Thromb. Vasc. Biol., March 1, 2006; 26(3): 563 - 569. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Cecil, K. Johnson, J. Rediske, M. Lotz, A. M. Schmidt, and R. Terkeltaub Inflammation-Induced Chondrocyte Hypertrophy Is Driven by Receptor for Advanced Glycation End Products J. Immunol., December 15, 2005; 175(12): 8296 - 8302. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Hermanns, A. A. Bertuch, T. K. Bertin, B. Dawson, M. E. Schmitt, C. Shaw, B. Zabel, and B. Lee Consequences of mutations in the non-coding RMRP RNA in cartilage-hair hypoplasia Hum. Mol. Genet., December 1, 2005; 14(23): 3723 - 3740. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. G. James, C. T. G. Appleton, V. Ulici, T. M. Underhill, and F. Beier Microarray Analyses of Gene Expression during Chondrocyte Differentiation Identifies Novel Regulators of Hypertrophy Mol. Biol. Cell, November 1, 2005; 16(11): 5316 - 5333. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. I. Pulai, H. Chen, H.-J. Im, S. Kumar, C. Hanning, P. S. Hegde, and R. F. Loeser NF-{kappa}B Mediates the Stimulation of Cytokine and Chemokine Expression by Human Articular Chondrocytes in Response to Fibronectin Fragments J. Immunol., May 1, 2005; 174(9): 5781 - 5788. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Johnson and R. A. Terkeltaub External GTP-bound Transglutaminase 2 Is a Molecular Switch for Chondrocyte Hypertrophic Differentiation and Calcification J. Biol. Chem., April 15, 2005; 280(15): 15004 - 15012. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Wang, Y. Ngalame, M. C. Panelli, H. Nguyen-Jackson, M. Deavers, P. Mueller, W. Hu, C. A. Savary, R. Kobayashi, R. S. Freedman, et al. Peritoneal and Subperitoneal Stroma May Facilitate Regional Spread of Ovarian Cancer Clin. Cancer Res., January 1, 2005; 11(1): 113 - 122. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
