Molekulare Techniken rheumatischer Krankheitsbilder

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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