Growth plate damage, a feature of juvenile idiopathic arthritis, can be induced by adenoviral gene transfer of oncostatin M: a comparative study in gene-deficient mice.
| Title: | Growth plate damage, a feature of juvenile idiopathic arthritis, can be induced by adenoviral gene transfer of oncostatin M: a comparative study in gene-deficient mice. |
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| Authors: | de Hooge AS; Rheumatology Research Laboratory, University Medical Center Nijmegen, Nijmegen Center for Molecular Life Sciences, Nijmegen, The Netherlands.; van de Loo FA; Bennink MB; Arntz OJ; Fiselier TJ; Franssen MJ; Joosten LA; Van Lent PL; Richards CD; van den Berg WB |
| Source: | Arthritis and rheumatism [Arthritis Rheum] 2003 Jun; Vol. 48 (6), pp. 1750-61. |
| Publication Type: | Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Wiley-Blackwell Country of Publication: United States NLM ID: 0370605 Publication Model: Print Cited Medium: Print ISSN: 0004-3591 (Print) Linking ISSN: 00043591 NLM ISO Abbreviation: Arthritis Rheum Subsets: MEDLINE |
| Imprint Name(s): | Publication: : Hoboken, N.J. : Wiley-Blackwell; Original Publication: Atlanta [etc.] Arthritis Foundation [etc.] |
| MeSH Terms: | Adenoviridae/*genetics ; Arthritis, Juvenile/*pathology ; Growth Plate/*pathology ; Peptides/*genetics; Arthritis, Juvenile/metabolism ; Interleukin-1/deficiency ; Interleukin-1/genetics ; Interleukin-1/metabolism ; Joints/metabolism ; Joints/pathology ; Peptides/metabolism ; Proteoglycans/metabolism ; RNA, Messenger/metabolism ; Synovial Fluid/metabolism ; Adolescent ; Animals ; Child ; Disease Models, Animal ; Female ; Gene Transfer Techniques ; Genetic Vectors ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Oncostatin M ; Reverse Transcriptase Polymerase Chain Reaction |
| Abstract: | Objective: To investigate the involvement of proinflammatory and destructive mediators in oncostatin M (OSM)-induced joint pathology, using gene-deficient mice.; Methods: An adenoviral vector expressing murine OSM was injected into the joints of naive wild-type mice and mice deficient for interleukin-1 (IL-1), IL-6, tumor necrosis factor alpha (TNFalpha), or inducible nitric oxide synthase (iNOS). Reverse transcription-polymerase chain reaction was used to study gene expression. Inflammation and cartilage proteoglycan (PG) depletion were assessed by histology. OSM and IL-1 levels in synovial fluid from patients with juvenile idiopathic arthritis (JIA) were measured by enzyme-linked immunosorbent assay.; Results: Adenoviral expression of murine OSM led to joint inflammation, bone apposition, chondrophyte formation, articular cartilage PG depletion, and VDIPEN neoepitope expression in wild-type mice. A unique and consistent observation was the focal PG depletion and disorganization of the growth plate cartilage during the first week of inflammation. Synovial IL-1beta, IL-6, TNFalpha, and iNOS gene expression was strongly induced. Of these factors, only deficiency in IL-1 markedly reduced inflammation and PG depletion and completely prevented growth plate damage. In addition, this is the first study in which OSM was detected in JIA synovial fluid. Most samples were also IL-1beta positive.; Conclusion: IL-1, but not IL-6, TNFalpha, or iNOS, plays an important role in joint disease induced by intraarticular gene transfer of OSM in mice. The effect of OSM on murine connective tissue and the presence of OSM in human synovial fluid make involvement of OSM in human arthropathies very likely. |
| Substance Nomenclature: | 0 (Interleukin-1); 0 (OSM protein, human); 0 (Osm protein, mouse); 0 (Peptides); 0 (Proteoglycans); 0 (RNA, Messenger); 106956-32-5 (Oncostatin M) |
| Entry Date(s): | Date Created: 20030610 Date Completed: 20030703 Latest Revision: 20131121 |
| Update Code: | 20260130 |
| DOI: | 10.1002/art.10972 |
| PMID: | 12794844 |
| Database: | MEDLINE |
Comparative Study; Journal Article; Research Support, Non-U.S. Gov't