RGD Reference Report - Midkine, a heparin-binding growth factor, is fundamentally involved in the pathogenesis of rheumatoid arthritis. - Rat Genome Database

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Midkine, a heparin-binding growth factor, is fundamentally involved in the pathogenesis of rheumatoid arthritis.

Authors: Maruyama, K  Muramatsu, H  Ishiguro, N  Muramatsu, T 
Citation: Maruyama K, etal., Arthritis Rheum. 2004 May;50(5):1420-9.
RGD ID: 1581200
Pubmed: PMID:15146411   (View Abstract at PubMed)
DOI: DOI:10.1002/art.20175   (Journal Full-text)

OBJECTIVE: Midkine (MK), a heparin-binding growth factor, promotes growth, survival, and migration of various cells. The essential role of MK in migration of inflammatory cells has been shown using mice deficient in the MK gene (Mdk(-/-) mice). We undertook this study to investigate the role of MK in the pathogenesis of rheumatoid arthritis (RA). METHODS: MK levels in specimens from patients were determined by enzyme-linked immunosorbent assay, and localization of MK was revealed by immunohistochemical analysis. Susceptibility to antibody-induced arthritis was compared between Mdk(-/-) and wild-type (WT) mice. Osteoclast differentiation was monitored using macrophage-like cells isolated from human synovial tissue and macrophages from mouse bone marrow. RESULTS: MK levels in sera and synovial fluid were increased in most RA patients, indicating a strong correlation between MK expression and RA. MK was expressed in macrophage-like cells and fibroblast-like cells in synovial membranes from the patients. In antibody-induced arthritis, Mdk(-/-) mice seldom developed the disease, while most of the WT mice did. Administration of MK to the Mdk(-/-) mice increased the frequency of antibody-induced arthritis. Migration of inflammatory leukocytes to the synovial membranes in the disease model was suppressed in the Mdk(-/-) mice. Furthermore, MK was found to promote the differentiation of osteoclasts from macrophages. CONCLUSION: MK participates in each of the two distinct phases of RA development, namely, migration of inflammatory leukocytes and osteoclast differentiation, and is a key molecule in the pathogenesis of RA.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
rheumatoid arthritis  ISOMdk (Mus musculus)1581200; 1581200 RGD 
rheumatoid arthritis  IAGP 1581200 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mdk  (midkine)

Genes (Mus musculus)
Mdk  (midkine)

Genes (Homo sapiens)
MDK  (midkine)


Additional Information