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Taurine ameliorates oxidative stress of BMSCs and promotes osteogenesis in irradiated jaws

ABSTRACT: Osteoradionecrosis of the jaw (ORNJ) is a complication after head and neck radiotherapy. Currently, an overall understanding of microenvironmental factors of ORNJ is still lacking. Here, we reveal the activation of taurine metabolism in irradiated mandibular stromal cells with scRNA-Seq and the decrease of taurine in irradiated bone marrow mesenchymal stromal cells (BMSCs) with metabolome. Compared to the unirradiated BMSCs, the taurine content of irradiated BMSCs decreases, and the taurine uptake increases. The taurine concentration in peripheral blood and jaws of irradiated mice are significantly lower than the unirradiated mice. Supplementation of taurine promotes osteogenic differentiation and decreases the generation of reactive oxygen species (ROS) of irradiated BMSCs. Oral administration of taurine significantly promotes osteogenesis of irradiated jaws and alleviates bone marrow fibrosis. Our study sheds light on the role of taurine during the recovery of radiation-induced jaw injury, suggesting a potential non-invasive therapeutic means to combat ORNJ.

ORGANISM(S): Mus musculus

PROVIDER: GSE269255 | GEO | 2024/11/18

REPOSITORIES: GEO

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Project description:Background: Metabolic dysregulation has been implicated in bronchopulmonary dysplasia development. Taurine is an essential amino acid for neonates and is critically involved in glucose and fatty acid metabolism. Neonatal tissue obtains taurine mainly through the taurine transporter. The biological role of taurine in neonatal lung development has never been explored. As glucose metabolism mechanistically modulates angiogenesis and angiogenesis is the central player for neonatal lung development, we hypothesize that taurine depletion contributes to bronchopulmonary dysplasia development. Results: Although most genes and proteins for oxidative phosphorylation were enriched in hyperoxia pup lungs, the complex-1 activity decreased. The decrease in taurine-dependent complex-1 core subunits, ND5 and ND6, in hyperoxia lungs reasonably explained the discrepancy. Metabolomics analysis demonstrated decreased lung taurine with increased blood taurine of hyperoxia pups, compatible with the decreased taurine transporter expression. Decreased glycosylation and increased degradation explained the decreased taurine transporter expression. The results of the complementary study using tunicamycin and tauroursodeoxycholic acid studies supported that endoplasmic reticulum stress contributes to decreased taurine transporter expression in hyperoxia lungs. The effect of taurine treatment on reducing endoplasmic reticulum stress, increasing ND5 and ND6 expression, angiogenesis, and, most importantly, the alveolar formation is beneficial to hyperoxia rat pups. Conclusion: Hyperoxia exposure causes endoplasmic reticulum stress, increases taurine transporter degradation, and leads to taurine depletion in the neonatal lungs with subsequent metabolic dysregulation, resulting in poor alveolar formation of the neonatal lungs. We provide evidence of the never-being-reported protective role of taurine in neonatal lung development. The fact that taurine attenuates the severity of bronchopulmonary dysplasia by reducing hyperoxia-induced endoplasmic reticulum stress and mitochondrial dysfunction indicates its therapeutic potential for treating bronchopulmonary dysplasia.

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Taurine ameliorates oxidative stress of BMSCs and promotes osteogenesis in irradiated jaws

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