PMID- 29156538 OWN - NLM STAT- MEDLINE DCOM- 20180702 LR - 20181113 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 18 IP - 11 DP - 2017 Nov 18 TI - Combined Effects of Simulated Microgravity and Radiation Exposure on Osteoclast Cell Fusion. LID - 10.3390/ijms18112443 [doi] LID - 2443 AB - The loss of bone mass and alteration in bone physiology during space flight are one of the major health risks for astronauts. Although the lack of weight bearing in microgravity is considered a risk factor for bone loss and possible osteoporosis, organisms living in space are also exposed to cosmic radiation and other environmental stress factors. As such, it is still unclear as to whether and by how much radiation exposure contributes to bone loss during space travel, and whether the effects of microgravity and radiation exposure are additive or synergistic. Bone is continuously renewed through the resorption of old bone by osteoclast cells and the formation of new bone by osteoblast cells. In this study, we investigated the combined effects of microgravity and radiation by evaluating the maturation of a hematopoietic cell line to mature osteoclasts. RAW 264.7 monocyte/macrophage cells were cultured in rotating wall vessels that simulate microgravity on the ground. Cells under static 1g or simulated microgravity were exposed to gamma rays of varying doses, and then cultured in receptor activator of nuclear factor-kappaB ligand (RANKL) for the formation of osteoclast giant multinucleated cells (GMCs) and for gene expression analysis. Results of the study showed that radiation alone at doses as low as 0.1 Gy may stimulate osteoclast cell fusion as assessed by GMCs and the expression of signature genes such as tartrate resistant acid phosphatase (Trap) and dendritic cell-specific transmembrane protein (Dcstamp). However, osteoclast cell fusion decreased for doses greater than 0.5 Gy. In comparison to radiation exposure, simulated microgravity induced higher levels of cell fusion, and the effects of these two environmental factors appeared additive. Interestingly, the microgravity effect on osteoclast stimulatory transmembrane protein (Ocstamp) and Dcstamp expressions was significantly higher than the radiation effect, suggesting that radiation may not increase the synthesis of adhesion molecules as much as microgravity. FAU - Shanmugarajan, Srinivasan AU - Shanmugarajan S AUID- ORCID: 0000-0001-8587-9402 AD - NASA Johnson Space Center, Houston, TX 77058, USA. srinimag@gmail.com. AD - Department of Biological and Environmental Sciences, University of Houston Clear Lake, Houston, TX 77058, USA. srinimag@gmail.com. FAU - Zhang, Ye AU - Zhang Y AD - NASA Kennedy Space Center, Cape Canaveral, FL 32899, USA. ye.zhang-1@nasa.gov. FAU - Moreno-Villanueva, Maria AU - Moreno-Villanueva M AD - NASA Johnson Space Center, Houston, TX 77058, USA. maria.moreno-villanueva@uni-konstanz.de. AD - Department of Biology, University of Konstanz, 78457 Konstanz, Germany. maria.moreno-villanueva@uni-konstanz.de. FAU - Clanton, Ryan AU - Clanton R AD - Department of Nuclear Engineering, Texas A & M University, College Station, TX 77843, USA. rc1025@tamu.edu. FAU - Rohde, Larry H AU - Rohde LH AD - Department of Biological and Environmental Sciences, University of Houston Clear Lake, Houston, TX 77058, USA. Rohde@uhcl.edu. FAU - Ramesh, Govindarajan T AU - Ramesh GT AD - Department of Biology, Norfolk State University, Norfolk, VA 23504, USA. gtramesh@nsu.edu. FAU - Sibonga, Jean D AU - Sibonga JD AD - NASA Johnson Space Center, Houston, TX 77058, USA. jean.sibonga-1@nasa.gov. FAU - Wu, Honglu AU - Wu H AD - NASA Johnson Space Center, Houston, TX 77058, USA. honglu.wu-1@nasa.gov. LA - eng PT - Journal Article DEP - 20171118 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Membrane Proteins) RN - 0 (RANK Ligand) RN - EC 3.1.3.2 (Acp5 protein, mouse) RN - EC 3.1.3.2 (Tartrate-Resistant Acid Phosphatase) SB - IM MH - Animals MH - Cell Culture Techniques MH - Cell Fusion MH - Cell Proliferation/radiation effects MH - Gene Expression Regulation/radiation effects MH - Macrophages/*cytology/metabolism/radiation effects MH - Membrane Proteins/*metabolism MH - Mice MH - Osteoclasts/*cytology/metabolism/radiation effects MH - RANK Ligand/pharmacology MH - RAW 264.7 Cells MH - Tartrate-Resistant Acid Phosphatase/*metabolism MH - Weightlessness/*adverse effects PMC - PMC5713410 OTO - NOTNLM OT - microgravity OT - osteoclast OT - radiation COIS- The authors declare no conflict of interest. EDAT- 2017/11/22 06:00 MHDA- 2018/07/03 06:00 PMCR- 2017/11/01 CRDT- 2017/11/22 06:00 PHST- 2017/10/07 00:00 [received] PHST- 2017/11/12 00:00 [revised] PHST- 2017/11/15 00:00 [accepted] PHST- 2017/11/22 06:00 [entrez] PHST- 2017/11/22 06:00 [pubmed] PHST- 2018/07/03 06:00 [medline] PHST- 2017/11/01 00:00 [pmc-release] AID - ijms18112443 [pii] AID - ijms-18-02443 [pii] AID - 10.3390/ijms18112443 [doi] PST - epublish SO - Int J Mol Sci. 2017 Nov 18;18(11):2443. doi: 10.3390/ijms18112443.