FUNCTIONAL GENOMIC RESEARCH IN OSTEOARTHRITIC CARTILAGE

Osteoarthritis (OA) is a common disabling degenerative disease of the joints.
Radiographic osteoarthritis in subject above 70 years is very prevalent (80%)
whereas in 2010 around 15% of the Dutch population will be above 65 years. The
OA phenotype is heterogeneous. Radiographic OA is characterized by joint space
narrowin and changes of the subchondral bone whereas clinically subjects suffer
of pain, stiffness and disability. Currently there is no drug available that is
able to slow down or stop the disease process. Eventulally, subjects with
advanced disease will become eligable for a joint replacement. So increased
knowledge on mechanism, prevention and adequate therapies on this degenerative
disease is a prerequisite to imporve the disease management.
It has been shown by various studies the genetic factors play on important role
in the onset of primary OA (without a clear cause). Identification of the genes
determing this heritabiliy alows insight in to the etiology of hte onset and
the progression of the disease. Recently, at the department of Molecular
Epidemiology new OA susceptibility genes involved in the thyroid pathway were
identified. The current protocol aims to collect bloed and joint tissue of OA
patients that undergo a joint replacement. From the blood and joint tissue we
will isolate genomic material (DNA en RNA) to proceed toward fucntional genomic
assays of thes genes.

The objective of the RAAK study is to collect bloed and joint tissue
(cartilage, ligaments and subchondral bone) of patients that undergo a total
joint replacement due to a endstage OA. Genomic material (DNA and RNA) will be
isolated from both the blood and joint tisse to investigate funtional effects
of the newly identified OA susceptibility genes. Increased knowledge on the
etiology of OA may eventually lead to the discovery of new drugable targets.

From patients that will undergo a joint replacement we will collect blood (1
EDTA tube (8ml) and 1 PAX gene tube (3 ml) and joint tissue during the
operation. The joint tissue will consist of the rest material that will come
available during the replacement. Bloed and tissue will be stored at the Dept.
of Molecular Epidemiology, LUMC. The genomic material will be isolated in time.
Long term storage of DNA and RNA and the research will occur at the department
of Molecular Epidemiologie.

There will very little burden and risk for participants of the study. In
addition there will be little short term, individual benefit.