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Osteoporosis and cardiovascular disease: new roles for the cholesterol sensing receptor, Liver X Receptor (LXR)
Kirsten Robertson, Ph.D.
Department of Biosciences and Nutrition at Novum, Karolinska Institutet
E-mail: [email protected]
Phone: 08-608 9160
Cardiovascular disease is the leading cause of morbidity and mortality in the Western world. Atherosclerosis is the most common underlying disease and is a chronic immune-inflammatory disease; involving local vascular injury, inflammation and alterations in lipid metabolism within the arterial wall. It has been shown that modified LDL taken up by the macrophage in the atherosclerotic lesion activates the Liver X Receptor, which then induces the expression of genes, such as the ABC transporters, to efflux this excess cholesterol to lipid poor lipoproteins (eg. ApoA1). This is an attempt by the macrophage to reduce the levels of intracellular cholesterol. Thus, the LXRs are proving to be an attractive target for the treatment of cardiovascular disease.
Osteoporosis is another one of the leading health problems in the aging population. It is the most common type of metabolic bone disease, affecting one in four women and one in eight men aged 50 and older. Both atherosclerosis and osteoporosis have been regarded as separate diseases that occur with aging. However, a large amount of evidence indicates that elevated LDL cholesterol and inflammation are common risk factors for both diseases.
Therefore, we chose to investigate if the LXRs are also important for bone development and function. Using the LXR knockout mouse model system, we have found that these nuclear receptors have specific roles in the formation and function of the bone resorbing cells; the osteoclasts.
The projects proposed here aim to characterise the mechanisms by which LXRα and LXRβ specifically affect osteoclast and osteoblast differentiation and function in the bone.
Specific projects can be discussed upon meeting, but techniques will include some of the following: cell culture, transfections, cloning, primary bone marrow cultures, immunohistochemistry, Real Time PCR, ELISA, mouse tissue studies.
Students with a keen interest in research and a good background in molecular biology and/or molecular medicine/physiology are welcome to apply. Feel free to contact me if you have any questions, or check our website: http://www.bionut.ki.se/groups/orphan/lxr/index.html
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