Projet de recherche PX/7/LP/07 (Action de recherche PX)
In normal adults, bone formation is in equilibrium with bone resorption. Skeletal unloading in humans and rats, as seen during spaceflight, induces a decrease in bone formation and a transient increase in bone resorption resulting in bone loss and compromised bone mechanical properties. Several experimental data indicate that osteoblasts function inappropriately in skeletal unloading or microgravity and that both osteoblast proliferation and differentiation are impaired. Understanding the underlying mechanisms of this process will certainly contribute to the prevention and treatment of space flight induced osteopenia but also to age-related osteoporosis.
The hypothesis tested in this project states that the response of bone to microgravity is (partly) osteoblast-mediated and that characterization of cellular alterations may help to understand the role of gravity in complex biological processes.
Recent experiments from our group and others have shown that altered gravity level not only affects osteoblast characteristics in vivo but also in vitro including changes in cell morphology as well as gene expression. We have shown that vitamin D induced differentiation of human osteoblastic cells, MG-63 cells, is impaired under microgravity conditions. In addition, microgravity alters the expression of growth factors in these cells. A plausible explanation for this microgravity-induced alteration is that the intracellular pathway by which vitamin D regulates gene expression is affected at a certain step by microgravity. Until now we could show that the interaction of the vitamin D receptor with its DNA response element was not affected by microgravity. Other possibilities remain to be investigated. Since space flight opportunities for in vitro experiments are rare we will use gene profiling to obtain extensive information on several pathways affected by vitamin D and microgravity.
In the planned microgravity experiments we aim to identify the molecular factors – known and unknown – that are differentially regulated in osteoblasts under microgravity conditions. We will use the mouse osteoblastic cell line MC3T3-E1 to confirm the previous findings on the human osteoblastic MG-63 cells and to extend these data using microarray analysis. Cluster analysis will be performed on the obtained data. Similar changes in the expression of different genes will suggest that a certain pathway is preferentially altered by microgravity.
Satellite(s) or flight opportunity(ies):
- Bolab on ISS
Field of research:
Life Science: Biology: Cell & Developmental Biology
Life Science: Human Physiology: Bone & Muscle Research
