Zusammenfassung
Die Analyse differentiell exprimierter Gene in multifaktoriellen Erkrankungen wie
der rheumatoiden Arthritis (RA) ist für die Entwicklung neuer Therapien von großer
Bedeutung. Die Analyse der Interaktionen zwischen den verschiedenen Zelltypen, der
Zellmatrix, intrazellulärer Signalwege sowie den Interaktionen der verschiedenen Gewebe
im Gelenk wie Knorpel, Knochen, Fettgewebe und dem Synovium tragen zum Verständnis
der Pathophysiologie der RA bei. Nicht nur die Identifizierung und Charakterisierung
neuer Moleküle zur Diagnose oder zur Beobachtung des Verlaufs der RA stehen im Vordergrund,
sondern auch die Analyse ihrer Wirkungsweisen, Funktion und Interaktionen. Funktionelle
Ansätze zur Genexpression basieren zumeist auf der Analyse von kultivierten synovialen
Zellen oder Geweben, wie z. B. von synovialen Fibroblasten, Chondrozyten, Makrophagen
oder Lymphozyten. Im Vordergrund stehen hierbei die molekularen Veränderungen oder
Pathomechanismen im RA-Synovium. In diesem Review sollen die verschiedenen Methoden
zur Analyse der Genexpression in Zellen und Geweben von Patienten mit Arthritiden
dargestellt und verglichen werden. Insbesondere wird hierbei auf mögliche Fehlerquellen
und Falschinterpretationen von Daten hingewiesen.
Abstract
The development of novel therapeutic approaches in multifactorial diseases such as
rheumatoid arthritis (RA), depends to a great extent on the analysis of differentially
regulated genes. The pathophysiology of RA, is best understood by examining the mechanisms
of interaction between different cell types, the cell matrix and intracellular signaling
pathways, as well as by examining the interactions between different tissues in the
joint such as cartilage, bone, adipose tissue and the synovium. The identification
and characterization of novel molecular markers plays a major role in diagnosing and
monitoring RA. Equally important, is the analysis of their function, mode of action
and interactions. Functional approaches to analyzing gene expression in arthritis
are currently based on examining cultured synovial cells or tissues, such as synovial
fibroblasts, chondrocytes, macrophages or lymphocytes, with emphasis on molecular
changes and pathomechanisms. In this review, different methods of analyzing gene expression
in cells and tissues from patients suffering from arthritis are presented and discussed.
In addition, a special focus engages in the pitfalls leading to misinterpretation
of the obtained data.
Schlüsselwörter
Molekulare Analyse - Rheumatoide Arthritis - Laser Mikrodissektion - siRNA - Fingerprint
- cDNA Array - Gentherapie - Proteomics - Molekulare Bildgebung
Key words
Molecular analysis - rheumatoid arthritis - laser microdissection - siRNA - fingerprinting
- cDNA array - gene therapy - proteomics - molecular imaging
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Dr. Elena Neumann
Justus-Liebig-Universität Gießen, Franz-Groedel-Institut, Kerckhoff-Klinik, Abt. Rheumatologie
und Klin. Immunologie
Benekestr. 2 - 8
61231 Bad Nauheim
Phone: ++ 49/60 32/9 96-28 01
Fax: ++ 49/60 32/9 96-28 09
Email: e.neumann@kerckhoff-klinik.de