title: 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.
authors.affiliation: Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA.
authors.forename: Xiangming
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA. Electronic address: ywang94@emory.edu.
authors.forename: Ya
authors.initials: Y
authors.lastname: Wang
mesh_terms: D015519:Bone Density; D001842:Bone and Bones; D002478:Cells, Cultured; D000071877:Checkpoint Kinase 1; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D006801:Humans; D010006:Osteoblasts; D010024:Osteoporosis; D010750:Phosphoproteins; D011839:Radiation, Ionizing; D014893:Weightlessness
chemical_list: D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D010750:Phosphoproteins; D000071877:Checkpoint Kinase 1
keywords: ASARM secretion; Bone density loss; CHK1; Ionizing radiation; MEPE; Microgravity