Skeletal metabolism and Stem Cells
Skeletal stem cells (SSCs) have the ability to differentiate into bone, cartilage and fat; the balance between bone and fat is disrupted in various human diseases. Different signaling pathways determine the fate of SSCs such as BMPs, Hh and Wnt.
This proposal addresses a less studied pathway mediating skeletal progenitors’ differentiation, PTH/PTHrP. DEPTOR is a key modulator of mTOR, a kinase that regulates cell growth and proliferation in response to environmental stimuli. Two skeletal dysplasias, Jansen Metaphyseal Chodrodysplasia (JMC) and Blomstrand Chondrodyplasia (BOCD), are produced by mutations in the PTH/PTHrP receptor.
This project led by Dr. Csukasi who studies DEPTOR as mediator in this metabolic alteration and its consequences on SSC differentiation.
1. DEPTOR related diseases
Recently our group (part of Krakow Lab in UCLA) described a new skeletal dysplasia caused by SIK3. We described in Science Translational Medicine a PTH-SIK3-mTOR signaling cascade essential for skeletogenesis mediated by DEPTOR. Our recent work identifies DEPTOR as an important modulator acting as a hinge with other signaling pathways that participates in the mechanism of disease of other skeletal dysplasias, cancer or metabolic disorders.
2. Skeletal Stem Cells and aging
One of the increasing health problems in our society is the one related with aging and stem cell exhaustion. Our group studies signaling pathways involved in the proliferation and differentiation of Skeletal Stem Cells (SSC) with the goal of reverting the loss of bone density into non-osteogenic lineages.
1. DEPTOR related diseases
Recently our group (part of Krakow Lab in UCLA) described a new skeletal dysplasia caused by SIK3. We described in Science Translational Medicine a PTH-SIK3-mTOR signaling cascade essential for skeletogenesis mediated by DEPTOR. Our recent work identifies DEPTOR as an important modulator acting as a hinge with other signaling pathways that participates in the mechanism of disease of other skeletal dysplasias, cancer or metabolic disorders.
2. Skeletal Stem Cells and aging
One of the increasing health problems in our society is the one related with aging and stem cell exhaustion. Our group studies signaling pathways involved in the proliferation and differentiation of Skeletal Stem Cells (SSC) with the goal of reverting the loss of bone density into non-osteogenic lineages.