A Novel Bone Shield to Improve Skeletal Health during Space Exploration and for Disuse Conditions on Earth.

Abstract

Bone loss due to disuse or mechanical unloading remains a significant space and Earth-based medical challenge to resolve. The efficacy of cerium oxide nanoparticles (CeONPs) to mitigate weightlessness-induced bone loss is unknown. Under gravity conditions in vitro, proteomic data reveal first evidence that during the early phase of osteogenesis, CeONPs augment osteoinduction, and osteoblast differentiation, survival, and proliferation via phosphoinositide 3-kinase protein kinase B signaling. CeONPs suppress adipogenic differentiation by regulating cellular energy metabolism, inhibiting adipose accumulation, and by upregulating proteins capable of directing osteo-adipogenic lineage fate toward osteogenesis over adipogenesis. Osteoclastogenesis is downregulated via c-Jun-N-terminal kinase, nuclear factor kappa B, epidermal growth factor receptor, and extracellular signal regulated kinase 1/2 pathways, and by the CeONP-mediated production of osteogenic factors within the osteoclast lineage cells. Following hind limb suspension (HLS), rapid, pathologic bone loss was measured in vivo. Notably, CeONP biodistribution reduced, potentially due to disadvantageous cephalad fluid shifts. Nevertheless, CeONP treatment buffers against oxidative stress, and significantly downregulates osteoclastic activation, bone resorption, bone marrow adiposity, and senescence, thereby maintaining a healthy bone structure despite HLS. These findings highlight CeONPs as a novel and promising therapeutic approach for addressing the skeletal challenges posed by microgravity and disuse conditions on Earth.