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Effects of space-relevant radiation on pre-osteoblasts

Hu, Yueyuan (2014) Effects of space-relevant radiation on pre-osteoblasts. Dissertation, Rheinische Friedrich-Wilhelms-Universität Bonn.

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Abstract

Until now limited research has been conducted to address the mechanisms leading ionizing radiation exposure induced bone loss. This is relevant for cancer radiotherapy and human spaceflight. Exposure to radiation can result in elevated bone fracture risk in patients receiving cancer radiotherapy. In human spaceflight, astronauts are exposed to space radiation which is a very complex mixture consisting primarily of high-energy charged particles. Osteoblasts are of mesenchymal origin and responsible for creating and maintaining skeletal architecture; these cells produce extracellular matrix proteins and regulators of matrix mineralization during initial bone formation and later bone remodeling. The aim of this work was to investigate the effects of ionizing radiation on pre-osteoblasts including cellular survival, cell cycle regulation and differentiation modification. Experiments with the pre-osteoblast cell line OCT-1 and the mesenchymal stem cell line C3H10T1/2 showed that radiation cell killing depends on dose and linear energy transfer (LET) and is most effective at an LET of ~150 keV/μm. High-LET radiation has a much more pronounced ability to induce cell cycle arrest in the G2/M phase. After both X-rays and heavy ions exposure, expression of the cell cycle regulator CDKN1A was significantly up-regulated in a dose-dependent manner. The findings suggest that cell cycle regulation is more sensitive to high-LET radiation than cell survival, which is not solely regulated through elevated CDKN1A expression. Radiation exposure enhances osteoblastic differentiation and maturation, and mediates Runx2 and TGF-β1 expression during early differentiation of pre-osteoblasts. Osteogenic differentiation did not alter cellular radiosensitivity, DNA repair of radiation-induced damages and the effects of radiation on proliferation. Further experiments are needed to elucidate possible synergistic effects of microgravity and radiation on osteoblast differentiation. This may provide the necessary foundation for the development for space travel countermeasures.

Item URL in elib:https://elib.dlr.de/89046/
Document Type:Thesis (Dissertation)
Title:Effects of space-relevant radiation on pre-osteoblasts
Authors:
AuthorsInstitution or Email of AuthorsAuthors ORCID iD
Hu, YueyuanDivision of Radiation Biology, Institute of Aerospace Medicine, German Aerospace Center (DLR), Linder Hoehe, 51147 Koeln, GermanyUNSPECIFIED
Date:2014
Refereed publication:Yes
Open Access:No
Gold Open Access:No
In SCOPUS:No
In ISI Web of Science:No
Number of Pages:136
Status:Published
Keywords:ionizing radiation, human spaceflight, cancer radiotherapy, pre-osteoblasts, cell cycle regulation, differentiation modification
Institution:Rheinische Friedrich-Wilhelms-Universität Bonn
Department:Mathematisch-Naturwissenschaftliche Fakultät
HGF - Research field:Aeronautics, Space and Transport
HGF - Program:Space
HGF - Program Themes:Research under Space Conditions
DLR - Research area:Raumfahrt
DLR - Program:R FR - Forschung unter Weltraumbedingungen
DLR - Research theme (Project):R - Vorhaben Strahlenbiologie
Location: Köln-Porz
Institutes and Institutions:Institute of Aerospace Medicine > Radiation Biology
Deposited By: Kopp, Kerstin
Deposited On:20 May 2014 15:43
Last Modified:20 May 2014 15:43

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