Reduced bone mass in senile osteoporotic patients has been associated with alterations in the differentiation capacity of resident bone marrow-derived mesenchymal stem cells (BMSCs) and has led to speculation that bone deterioration associated with age-related osteoporosis may be directly related to an inability to produce a sufficient number of functionally active osteoblasts.
One of our aims therefore is to characterize the functional role played by BMSCs in the development of osteoporotic bone through the use of molecular, biochemical and histological techniques. We are currently utilizing stem cells isolated from both human patients and experimental models and have developed the necessary techniques with which to successfully harvest and expand cells from specific stem cell niches.
Differentiation of mesenchymal stem cells is an essential requirement for the homeostatic control of the bone multicellular unit. We are interested in understanding how deviations in the differentiation pathway may lead to alterations in bone quality, such as those observed in osteoporosis. (picture left:oil red O staining of adipocyte)
Cellular Ageing is thought to play a key role in a variety of disease pathologies. Alterations in the biological ageing of cells can be determined though the use of various techniques including Q-FISH. We are currently using this method to investigate the involvement of cellular ageing in the pathogenesis of bone disease. (picture left: Q-FISH analysis of undifferentiated MSCs)
Serine protease HTRA1 is thought to play an important role in a variety of normal and pathological conditions affecting the musculoskeletal system. We are currently investigating its involvement in bone development and regeneration through its ability to influence BMSC differentiation (picture left: HTRA1 immunostain (brown) in regenerating bone)