Radiation activated CHK1/MEPE pathway may contribute to microgravity-induced bone density loss

Abstract

Bone density loss in astronauts on long-term space missions is a chief medical concern. Microgravity in space is the major cause of bone density loss (osteopenia), and it is believed that high linear energy transfer (LET) radiation in space exacerbates microgravity-induced bone density loss; however, the mechanism remains unclear. It is known that acidic serine- and aspartate-rich motif (ASARM) as a small peptide released by matrix extracellular phosphoglycoprotein (MEPE) promotes osteopenia. We previously discovered that MEPE interacted with checkpoint kinase 1 (CHK1) to protect CHK1 from ionizing radiation promoted degradation. In this study, we addressed whether the CHK1-MEPE pathway activated by radiation contributes to the effects of microgravity on bone density loss. We examined the CHK1, MEPE and secreted MEPE/ASARM levels in irradiated (1 Gy of X-ray) and rotated cultured human osteoblast cells. The results showed that radiation activated CHK1, decreased the levels of CHK1 and MEPE in human osteoblast cells and increased the release of MEPE/ASARM. These results suggest that the radiation-activated CHK1/MEPE pathway exacerbates the effects of microgravity on bone density loss, which may provide a novel targeting factor/pathway for a future countermeasure design that could contribute to reducing osteopenia in astronauts.

The combined effects of simulated microgravity and X-ray radiation on MC3T3-E1 cells and rat femurs

“…Limited osteoblast cell research has evaluated the combined effect. X-ray RA exacerbated the effects of MG on bone density loss, cell proliferation, and mineralization decreased combined high-frequency acoustic wave signals and increased combined low-intensity pulsed ultrasound in a simulated MG environment 33,34 . In this study, in MC3T3-E1 cells, the combination of RA and MG also exacerbated the decreased osteoblast differentiation and increased osteoblast apoptosis, induced by the individual treatments, and the exact underlying mechanism requires further research.…”