Functional evaluation of the role of LRP4 and NPR3 in the regulation of bone metabolism by regulating respectively bone mass and bone growth.

Bone metabolism is a complex process which is not only important during the development of the skeleton with the regulation of bone growth but also throughout life to maintain bone mass and bone strength. In our research group, we investigate the genetic cause of several skeletal dysplasias marked by abnormal bone mass or growth. In the past, this already resulted in the identification of several disease causing genes. With this project, we aim to further elucidate the role of two of these disease causing genes, namely LRP4 and NPR3, in the regulation of respectively bone mass and bone growth. Lrp4 is a modulator of the canonical WNT signaling pathway which is well known for its role in the regulation of bone formation. Previous to this project, we generated and phenotypically characterized a mouse model with a mutation in Lrp4. As this mouse has a highly increased bone mass, we aim to further elucidate the mechanism whereby LRP4 regulates bone formation by performing additional in vitro and in vivo studies. In addition, more recently, we demonstrated that loss of function mutations in NPR3 result in skeletal overgrowth among other features. Since in literature, three different functions are described for the NPR3 receptor, we aim to further investigate the role of NPR3 in the regulation of the natriuretic signaling pathway and bone growth by performing several in vitro experiments. We believe that this study will increase the insights into regulation of bone metabolism.

Keywords:BONE METABOLISM

Disciplines:Laboratory medicine, Medical systems biology, Molecular and cell biology