Effects of exposure to space relevant radiation on the differentiation and mineralization process of murine osteoblastic cell lines

Abstract

During spaceflight, astronauts experience both solar and galactic cosmic radiation as well as the absence of gravity, especially during planned long term missions to Moon and Mars. Potential deleterious effects under these conditions include specific impact on the skeletal, central nervous and immune systems as well as the induction of cancer. However, until now little is known about the effects of space radiation on bone cells, especially on the bone forming osteoblasts. Heavy ion accelerators are ground based facilities, used to simulate single components of the radiation environment in space. Within our experimental setup we examined the cellular survival as well as the differentiation and mineralization capacities of osteoblastic cell lines after exposure to carbon ( C-13 75MeV/A), neon ( Ne-22 80 MeV/A), and nickel ions ( Ni-58 1 GeV/A) in comparison to low LET X-rays. Modifications in the differentiation process were monitored by measuring mRNA expression levels of osteocalcin, a key marker of osteoblastic differentiation and transforming growth factor-β1 (TGF-β1) which offers an important role during bone remodeling. Additionally, the mineralization process after radiation exposure was quantified after staining of hydroxyapatite containing bone-like nodules deposited by osteoblastic cells. The results suggest that ionizing radiation significantly modulates the differentiation process and effectively modulates the gene expression levels of marker genes involved in the differentiation of osteoblasts. In conclusion, the presented data allow the suggestion that exposure to heavy ions interferes with bone formation at the level of cell differentiation. Further experiments are needed to investigate gene expression patterns in mammalian cells that respond to differentiation after exposure to high LET radiation.