Taurine ameliorates oxidative stress of BMSCs and promotes osteogenesis in irradiated jaws
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PROVIDER: PRJNA1120832 | ENA |
REPOSITORIES: ENA
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Project description: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.
2024-11-18 | GSE269255 | GEO
Project description:Osteoradionecrosis of the jaw (ORNJ) is a complication after head and neck radiotherapy that severely affects patients’ quality of life. 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 metabolomics. Compared to the unirradiated BMSCs, the taurine uptake of irradiated BMSCs 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, decreases oxidative stress and DNA damage of irradiated BMSCs. Oral administration of taurine significantly promotes survival rate of irradiated mice and promotes osteogenesis of irradiated jaws. 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.
2024-07-08 | MTBLS10284 | MetaboLights
Project description:The pathogenesis of osteoporosis (OP) is closely associated with the disrupted balance between osteogenesis and adipogenesis in bone marrow-derived mesenchymal stem cells (BMSCs). We analyzed published single-cell RNA sequencing (scRNA-seq) data to dissect the transcriptomic profiles of bone marrow-derived cells in OP, reviewing 56,377 cells across eight scRNA-seq datasets from femoral heads (osteoporosis or osteopenia n=5, osteoarthritis n=3). Seventeen genes, including carboxypeptidase M (CPM), were identified as key osteogenesis-adipogenesis regulators through comprehensive gene set enrichment, differential expression, regulon activity, and pseudotime analyses. In vitro, CPM knockdown reduced osteogenesis and promoted adipogenesis in BMSCs, while adenovirus-mediated CPM overexpression had the reverse effects. In vivo, intraosseous injection of CPM-overexpressing BMSCs mitigated bone loss in ovariectomized mice. Integrated scRNA-seq and bulk RNA sequencing analyses provided insight into the MAPK/ERK pathway's role in the CPM-mediated regulation of BMSC osteogenesis and adipogenesis; specifically, CPM overexpression enhanced MAPK/ERK signaling and osteogenesis. In contrast, the ERK1/2 inhibitor binimetinib negated the effects of CPM overexpression. Overall, our findings identify CPM as a pivotal regulator of BMSC differentiation, which provide new clues for the mechanistic study of OP.
2023-12-14 | GSE249471 | GEO
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.
2024-06-01 | GSE249767 | GEO
Project description:In this study, we found that Fgf9 regulates the bone-fat balance by modulating the cell fate determination of BMSCs. Histology and micro-CT analysis demonstrate that Fgf9 S99N mutation (loss-of-function) significantly inhibited the formation of bone marrow adipose tissue (BMAT) in adult mice and alleviated the ovariectomized (OVX) induced bone loss and BMAT accumulation. In vitro cytodifferentiation assays unveiled that the Fgf9 S99N mutation hindered adipogenesis while promoting osteogenesis in BMSCs. Furthermore, recombinant FGF9 stimulation and Fgf9 overexpression in BMSCs demonstrated that Fgf9 significantly promoted adipocyte formation and inhibited osteogenesis in vitro and in vivo. Cytodifferentiation assays at various stages of BMSC differentiation indicated that FGF9 altered the osteogenic and adipogenic potential of BMSCs, particularly during the early stages of differentiation. Transcriptomic and gene expression analyses demonstrated that FGF9 significantly upregulated the expression of adipogenic genes while downregulating osteogenic gene expression at both mRNA and protein levels. KEEG analysis revealed and in vitro differentiation assays with specific inhibitors confirmed that FGF9 modulated bone-fat balance by inhibiting osteogenesis via the MAPK/ERK pathway and promoting adipogenesis by activating the PI3K/AKT and Hippo pathways.
2024-07-17 | GSE252394 | GEO
Project description:Rationale：Poor peri-implant osseointegration of dental implants in patients with type II diabetes has become a major clinical challenge in recent years. MSC (Mesenchymal stem cell)-derived exosomes may play an important role in peri-implant osseointegration, but the mechanism remains unclear. Enhancing the therapeutic effect of MSC-derived exosomes and exploring the potential mechanism can help provide a new therapeutic strategy to improve the clinical outcome of dental implant restorations in patients with type II diabetes. Methods：The exosomes derived from hypoxia (Hypo-exos) or normoxia (Nor-exos) preconditioned bone marrow mesenchymal stem cells (BMSCs) were co-cultured with BMSCs and human umbilical vein endothelial cells (HUVECs). The effect of exosomes on BMSCs cell proliferation was detected by CCK-8 assay and EdU assay, and the effect on angiogenesis ability of HUVECs was detected by wound healing assay, transwell migration assay, tube formation assay, enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. A diabetic rat dental implant model was also established and the effect of exosomes on implant osseointegration was evaluated through micro-CT scanning and histological analysis. The differentially expressed miRNAs between Hypo-exos and Nor-exos were identified by high-throughput miRNA sequencing. Subsequently, the target genes and their roles in regulating angiogenesis were predicted and analyzed by bioinformatics analysis and dual luciferase reporter assay. Results：In vitro experiments indicated that hypoxia preconditioning could elevate exosome production and promote cell proliferation of BMSCs and angiogenesis of HUVECs. Moreover, Hypo-exos promoted peri-implant osteogenesis in rats with diabetes. Further investigation revealed the vital involvement of the miR-106b-5p/HIF-1α axis in promoting peri-implant osseointegration. Conclusion: Exosomes derived from hypoxia-preconditioned BMSCs could improve the peri-implant osseointegration in rats with diabetes by promoting cell proliferation and angiogenesis, and the miR-106b-5p/ HIF-1α axis could be the underlying mechanism.
2024-09-04 | GSE275863 | GEO
Project description:During the aging process, bone marrow mesenchymal stem cells (BMSCs) exhibit declined osteogenesis accompanied by excess adipogenesis, which will lead to osteoporosis. Here we report that the H3K36 trimethylation, catalyzed by histone methyltransferase SETD2 regulates lineage commitment of BMSCs. Deletion of Setd2 in mBMSCs, through conditional Cre expression driven by Prx1 promoter, resulted in bone loss and marrow adiposity. Loss of Setd2 in BMSCs in vitro facilitated differentiation propensity to adipocytes rather than to osteoblasts. Through conjoint analysis of RNA-seq and ChIP-seq data, we identified a SETD2 functional target gene, Lbp, on which H3K36me3 was enriched, and its expression was affected by Setd2 deficiency. Furthermore, overexpression of LBP could partially rescue the lack of osteogenesis and enhanced adipogenesis resulted from the absence of Setd2 in BMSCs. Further mechanism study demonstrated that the trimethylation level of H3K36 could regulate Lbp transcriptional initiation and elongation. These findings suggest that H3K36 trimethylation mediated by SETD2 could regulate the cell fate of mesenchymal stem cells in vitro and in vivo, indicating that the regulation of H3K36me3 level by targeting SETD2 and/or the administration of downstream LBP protein may represent potential therapeutic way for new treatment in metabolic bone diseases, such as osteoporosis.
2018-11-08 | GSE120351 | GEO
Project description:During the aging process, bone marrow mesenchymal stem cells (BMSCs) exhibit declined osteogenesis accompanied by excess adipogenesis, which will lead to osteoporosis. Here we report that the H3K36 trimethylation, catalyzed by histone methyltransferase SETD2 regulates lineage commitment of BMSCs. Deletion of Setd2 in mBMSCs, through conditional Cre expression driven by Prx1 promoter, resulted in bone loss and marrow adiposity. Loss of Setd2 in BMSCs in vitro facilitated differentiation propensity to adipocytes rather than to osteoblasts. Through conjoint analysis of RNA-seq and ChIP-seq data, we identified a SETD2 functional target gene, Lbp, on which H3K36me3 was enriched, and its expression was affected by Setd2 deficiency. Furthermore, overexpression of LBP could partially rescue the lack of osteogenesis and enhanced adipogenesis resulted from the absence of Setd2 in BMSCs. Further mechanism study demonstrated that the trimethylation level of H3K36 could regulate Lbp transcriptional initiation and elongation. These findings suggest that H3K36 trimethylation mediated by SETD2 could regulate the cell fate of mesenchymal stem cells in vitro and in vivo, indicating that the regulation of H3K36me3 level by targeting SETD2 and/or the administration of downstream LBP protein may represent potential therapeutic way for new treatment in metabolic bone diseases, such as osteoporosis.
2018-11-08 | GSE120244 | GEO
Project description:Analysis of skeletal muscle from taurine transporter (TauT) knockout mice at 3 or 18 months of age. Knocking out TauT result in a decrease in muscle cell size, impaired exercise capacity and accelerated muscle aging. Results provide molecular insights into physiological role of taurine. Sample: 12
2014-05-08 | E-GEOD-57373 | biostudies-arrayexpress
Project description:Analysis of skeletal muscle from taurine transporter (TauT) knockout mice at 3 or 18 months of age. Knocking out TauT result in a decrease in muscle cell size, impaired exercise capacity and accelerated muscle aging. Results provide molecular insights into physiological role of taurine.
2014-05-08 | GSE57373 | GEO