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The role of transforming growth factor β signaling in fibroblast-like synoviocytes from patients with oligoarticular juvenile idiopathic arthritis: dysregulation of transforming growth factor β signaling, including overexpression of bone morphogenetic protein 4, may lead to a chondrocyte phenotype and may contribute to bony hypertrophy.
- Source :
-
Arthritis & rheumatology (Hoboken, N.J.) [Arthritis Rheumatol] 2014 May; Vol. 66 (5), pp. 1352-62. - Publication Year :
- 2014
-
Abstract
- Objective: This study was designed to investigate the pathogenic contributions of fibroblast-like synoviocytes (FLS) to juvenile idiopathic arthritis (JIA) by identifying pathways with dysregulated gene expression in FLS from patients with oligoarticular JIA.<br />Methods: FLS were derived from synovial fluid obtained by arthrocentesis from patients with JIA undergoing intraarticular steroid injections and from orthopedic control patients. Gene expression profiles of the JIA and control FLS were obtained using the Affymetrix platform, with application of Ingenuity Pathway Analysis and Gene Set Enrichment Analysis software to define gene sets in dysregulated pathways and networks of potential pathologic relevance in this disease. Biologically relevant differentially expressed genes were confirmed by RNA and protein analysis.<br />Results: Exploration of global gene expression profiles of the JIA FLS revealed important dysregulated pathways, including the transforming growth factor β (TGFβ) signaling, as well as endochondral bone formation, cartilage formation, and β-catenin networks. Importantly, bone morphogenetic protein 4 (BMP-4) was significantly overexpressed in the JIA FLS. FLS from patients with oligoarticular JIA exhibit a chondrocyte phenotype, as evidenced by expression of type II collagen and aggrecan.<br />Conclusion: Dysregulation of the pathways involved in the pathogenesis of oligoarticular JIA were revealed through gene expression profiling. JIA FLS displayed dysregulated TGFβ signaling and exhibited a hypertrophic chondrocyte phenotype. These characteristics, along with contributions from the β-catenin network may have implications for endochondral bone formation and local growth disturbances in oligoarticular JIA. Overexpression of BMP-4 in FLS from patients with oligoarticular JIA in particular may play an important role in disease pathogenesis, with a direct effect on functional outcome and with implications for future treatment.<br /> (© 2014 The Authors. Arthritis & Rheumatology is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.)
- Subjects :
- Adolescent
Aggrecans genetics
Aggrecans metabolism
Arthritis, Juvenile pathology
Arthritis, Juvenile physiopathology
Bone Morphogenetic Protein 4 genetics
Case-Control Studies
Cell Differentiation physiology
Child
Child, Preschool
Chondrocytes metabolism
Collagen Type II genetics
Collagen Type II metabolism
Female
Gene Expression Profiling
Humans
Hyperostosis pathology
Hyperostosis physiopathology
Male
Osteogenesis physiology
Synovial Fluid metabolism
Synovial Membrane pathology
Transforming Growth Factor beta genetics
beta Catenin genetics
beta Catenin metabolism
Arthritis, Juvenile metabolism
Bone Morphogenetic Protein 4 metabolism
Chondrocytes pathology
Hyperostosis metabolism
Phenotype
Signal Transduction physiology
Synovial Membrane metabolism
Transforming Growth Factor beta metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2326-5205
- Volume :
- 66
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Arthritis & rheumatology (Hoboken, N.J.)
- Publication Type :
- Academic Journal
- Accession number :
- 24782191
- Full Text :
- https://doi.org/10.1002/art.38336