7 Frame

This project is supported through Coordination Theme 1 (Health) of the European Community's FP7. Grant agreement number HEALTH-F2-2008-00

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Work Package 7

logoWP 7: Functional Genomics: in vivo studies and animal models of OA

Participants:

Oxford, KU Leuven

Objectives:

  1. To test the role of selected genes in osteoarthritis in mice and to develop new genetic mouse models for OA that will facilitate the investigation of the pathogenesis of OA and provide models in which novel therapeutic targets can be tested.
  2. To screen the large-scale random N-ethylnitrosourea (ENU) mutagenesis resources established for mouse (WP7.1) and test selected genes in established postnatal models of OA triggered by instability, direct cartilage damage or inflammation in mice. (WP7.2).

Status:

In workpackage 7.2, we studied the roles of different genes in the development of osteoarthritis in specific animal models. These genes, including Frzb, have been identified by the genetic screens. Mice with targeted deletion or overexpression of these genes are studied in different models: collagenase induced osteoarthritis, papain induced osteoarthritis, antigen induced arthritis, osteoarthritis caused by destabilization of the medial meniscus and strain protocols. The systematic analysis based on histomorphological, imaging and molecular approaches allows the researcher to dissect the roles these genes are likely to play in the different tissues of the joint in homeostasis and disease.

Publications:

  • Wnt signaling and osteoarthritis. Luyten FP, Tylzanowski P, Lories RJ. Bone. 2009 Apr;44(4):522-7. Epub 2008 Dec 14.
  • Articular cartilage and biomechanical properties of the long bones in Frzb-knockout mice. Lories RJ, Peeters J, Bakker A, Tylzanowski P, Derese I, Schrooten J, Thomas JT, Luyten FP. Arthritis Rheum. 2007 Dec;56(12):4095-103.
  • Contemporary concepts of inflammation, damage and repair in rheumatic diseases. Luyten FP, Lories RJ, Verschueren P, de Vlam K, Westhovens R. Best Pract Res Clin Rheumatol. 2006 Oct;20(5):829-48.
  • Noggin haploinsufficiency differentially affects tissue responses in destructive and remodeling arthritis. Lories RJ, Daans M, Derese I, Matthys P, Kasran A, Tylzanowski P, Ceuppens JL, Luyten FP. Arthritis Rheum. 2006 Jun;54(6):1736-46.
  • Bone morphogenetic protein signaling in joint homeostasis and disease. Lories RJ, Luyten FP. Cytokine Growth Factor Rev. 2005 Jun;16(3):287-98.