Total body irradiation (TBI) can impair the bone marrow (BM) microenvironment and dysregulate the fates of BM-residing cells by overproducing reactive oxygen species (ROS) and inflammatory mediators. This study aims to investigate the potency and mechanism of Deinococcus radiodurans-derived deinoxanthin (DEIX) in mitigating TBI-mediated injuries in the BM microenvironment and BM-resident cells. C57BL/6 mice were divided into control, TBI, TBI+DEIX, and/or DEIX groups, in which the mice were exposed to sub-lethal TBI (5 Gy) or in combination with oral DEIX supplementation (25 mg/kg body weight). While the DEIXs effect on BM and BM-resident cells was determined after five weeks of TBI, RNA sequence profiling on the mouse group-derived BM cells was performed after two weeks of TBI. Supplementation with DEIX protected mice against TBI-mediated decrease in bone mineral density of trabecular bones. Supplemental DEIX suppressed BM microenvironmental impairment and the induction of oxidative stress and senescence in BM cells of TBI-exposed mice. That suppression was orchestrated by the DEIX-induced restoration of TBI-stimulated disorders in osteogenic, osteoclastogenic, and adipogenic activation in the BM. Ex vivo assays using BM cells supported the notion that DEIX restores TBI-mediated defects in BM cell function, including colony formation, migration, and differentiation. RNA sequence profiling demonstrated DEIXs potency to modulate the expression of genes that regulate cellular and systemic immune responses, cell proliferation and differentiation, and bone metabolism. Collectively, our results highlight the roles and associated mechanisms of DEIX in mitigating TBI-mediated microenvironmental impairment and in regulating BM-resident cells.
Rijal, S., Kim, K., Bhattarai, G., Kim, B., Kim, J., Jeon, Y.-M., Kiook, S.-H., Lee, J.-C.
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