Mechanism of glycosaminoglycan-mediated bone and joint disease: implications for the mucopolysaccharidoses and other connective tissue diseases.

Mechanism of glycosaminoglycan-mediated bone and joint disease: implications for the mucopolysaccharidoses and other connective tissue diseases. Research Abstract Details 

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Mechanism of glycosaminoglycan-mediated bone and joint disease: implications for the mucopolysaccharidoses and other connective tissue diseases. Abstract Text:

Calogera M Simonaro,Marina D'Angelo,Xingxuan He,Efrat Eliyahu,Nataly Shtraizent,Mark E Haskins,Edward H Schuchman,Calogera M Simonaro,Marina D'Angelo,Xingxuan He,Efrat Eliyahu,Nataly Shtraizent,Mark E Haskins,Edward H Schuchman,Calogera M Simonaro,Marina D'Angelo,Xingxuan He,Efrat Eliyahu,Nataly Shtraizent,Mark E Haskins,Edward H Schuchman,

We have previously shown that glycosaminoglycan (GAG) storage in animal models of the mucopolysaccharidoses (MPS) leads to inflammation and apoptosis within cartilage. We have now extended these findings to synovial tissue and further explored the mechanism underlying GAG-mediated disease. Analysis of MPS rats, cats, and/or dogs revealed that MPS synovial fibroblasts and fluid displayed elevated expression of numerous inflammatory molecules, including several proteins important for lipopolysaccharide signaling (eg, Toll-like receptor 4 and lipoprotein-binding protein). The expression of tumor necrosis factor, in particular, was elevated up to 50-fold, leading to up-regulation of the osteoclast survival factor, receptor activator of nuclear factor-kappaB ligand, and the appearance of multinucleated osteoclast-like cells in the MPS bone marrow. Treatment of normal synovial fibroblasts with GAGs also led to production of the prosurvival lipid sphingosine-1-phosphate, resulting in enhanced cell proliferation, consistent with the hyperplastic synovial tissue observed in MPS patients. In contrast, GAG treatment of normal chondrocytes led to production of the proapoptotic lipid ceramide, confirming the enhanced cell death we had previously observed in MPS cartilage. These findings have important implications for the pathogenesis and treatment of MPS and have further defined the mechanism of GAG-stimulated disease.

Mechanism of glycosaminoglycan-mediated bone and joint disease: implications for the mucopolysaccharidoses and other connective tissue diseases. Publishing Authors By Initials

CM Simonaro,M D'Angelo,X He,E Eliyahu,N Shtraizent,ME Haskins,EH Schuchman,CM Simonaro,M D'Angelo,X He,E Eliyahu,N Shtraizent,ME Haskins,EH Schuchman,CM Simonaro,M D'Angelo,X He,E Eliyahu,N Shtraizent,ME Haskins,EH Schuchman,

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Mechanism of glycosaminoglycan-mediated bone and joint disease: implications for the mucopolysaccharidoses and other connective tissue diseases. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: The American journal of pathology

VOLUME: 172

Page Numbers: 112-22

Journal Abbreviation: Am. J. Pathol.

ISSN: 0002-9440

DAY: 13

MONTH: 12

YEAR: 2007

Mechanism of glycosaminoglycan-mediated bone and joint disease: implications for the mucopolysaccharidoses and other connective tissue diseases. Information

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LANGUAGE: eng

NlmUniqueID: 370502

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AFFILIATION: Associate Professor, Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, 1425 Madison Ave., New York, NY, 10029. calogera.simonaro@mssm.edu.

Country: United States

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MEDLINETA: Am J Pathol

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