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.

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.

• Authors: Alfons S K de Hooge, Fons A J van de Loo, Miranda B Bennink, Onno J Arntz, Theo J W Fiselier, Marcel J A M Franssen, Leo A B Joosten, Peter L E M Van Lent, Carl D Richards, Wim B van den Berg
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 48 Issue 6 Pg. 1750-61 (Jun 2003) ISSN: 0004-3591 [Print] United States
• PMID: 12794844 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-1
• OSM protein, human
• Osm protein, mouse
• Peptides
• Proteoglycans
• RNA, Messenger
• Oncostatin M

Topics

• Adenoviridae (genetics)
• Adolescent
• Animals
• Arthritis, Juvenile (metabolism, pathology)
• Child
• Disease Models, Animal
• Female
• Gene Transfer Techniques
• Genetic Vectors
• Growth Plate (pathology)
• Humans
• Interleukin-1 (deficiency, genetics, metabolism)
• Joints (metabolism, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Oncostatin M
• Peptides (genetics, metabolism)
• Proteoglycans (metabolism)
• RNA, Messenger (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Synovial Fluid (metabolism)