The prevalence of iron overload in Tibetans in Tibet is higher than that in Han. DNA methylation (DNAm) is closely related to iron metabolism and iron level. Nevertheless, the epigenetic status of Tibetans with iron overload is unknown, and we therefore aimed to explore whether the phenomenon observed in the Tibetan population is regulated by epigenetics. The results showed that 2.26% of cytosine was methylated in the whole genome, and that the rate of CG cytosine methylation was higher in individuals in the iron overload (TH) group than in those in the iron normal (TL) group. We analyzed differentially methylated genes (DMGs) in whole-genome bisulfite sequencing data from the TH and TL groups of high-altitude Tibetans. Protein-protein interaction and pathway analyses of candidate DMGs related to iron uptake and transport showed that epigenetic changes in 10 candidate genes (ACO1, CYBRD1, FLVCR1, HFE, HMOX2, IREB2, NEDD8, SLC11A2, SLC40A1 and TFRC) are likely to relate to iron overload. This work reveals, for the first time, changes of DNAm in Tibetan people with iron overload, which suggest that DNAm is a mechanism underlying differences in iron content between individuals in the high-altitude Tibetan population. Our findings should contribute to the study of iron metabolism and the overall health status of Tibetans.

Objective Stem-cell therapy is a promising treatment for cartilage defects. The newly identified urine-derived stem cells (USCs), which have multipotency and sufficient proliferative ability, are promising candidates for several tissue engineering therapies. In this study, we investigated the role of USC extracellular vehicles (EVs) in promoting the proliferation and migration of chondrocytes. Design USCs were characterized by measuring induced multipotent differentiation and flow cytometry analysis of surface marker expression. The EVs were isolated from USCs under normoxic conditions (nor-EVs) and hypoxic conditions (hypo-EVs). Transmission electron microscopy and western blot analysis characterized the EVs. The chondrocytes were cultured in the USC-EVs. CCK-8 assay and EdU staining detected the proliferation of chondrocytes, and transwell assay detected their migration. miR-26a-5p expression in EVs was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The target relationship of miR-26a-5p and phosphatase and tensin homolog (PTEN) was predicted and confirmed. The roles of EVs-miR-26a-5p and PTEN on the proliferation and migration of chondrocytes were also investigated. Results Hypo-EVs showed a superior effect in promoting the proliferation and migration of chondrocytes than nor-EVs. Mechanistically, USC-EVs delivered miR-26a-5p into chondrocytes to overexpress miR-26a-5p. PTEN was identified as an miR-26a-5p target in chondrocytes. The effects of EVs-miR-26a-5p on promoting the proliferation and migration of chondrocytes were mediated by its regulation of PTEN. Conclusion Our study suggested that hypoxic USC-EVs may represent a promising strategy for osteoarthritis by promoting the proliferation and migration of chondrocytes via miR-26a-5p transfer.

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Iron overload can lead to chronic complications, serious organ dysfunction or death in the body. Under hypoxic conditions, the body needs more iron to produce red blood cells to adapt to the hypoxic environment. The prevalence of iron overload in the Tibetan population is higher than that in the Han population. To explore the molecular mechanism of ironoverload in the Tibetan population, this study investigated the transcriptome of the Tibetan iron overload population to obtain differentially expressed genes (DEGs) between the iron-overloaded population and the normal iron population. Functional enrichment analysis identified key related pathways, gene modules and coexpression networks under iron-overload conditions, and the 4 genes screened out have the potential to become target genes for studying the development of iron overload. A total of 28 pathways were screened to be closely related to the occurrence and development of iron overload, showing that iron overload is extremely related to erythrocyte homeostasis, cell cycle, oxidative phosphorylation, immunity, and transcriptional repression.