Gut microbiota and osteonecrosis: A Mendelian randomization study

Medicine, Journal Year: 2025, Volume and Issue: 104(10), P. e41703 - e41703

Published: March 7, 2025

Emerging evidence indicates an association between the gut microbiota and incidence of osteonecrosis (ON), yet literature has not adequately addressed whether this relationship is causal. This study uses data from MiBioGen Consortium UK Biobank for Mendelian randomization (MR) analysis to identify pathogenic microbial taxa associated with ON. Sensitivity analyses confirmed causal relationships, while reverse MR ruled out causation. SNP annotation located genetic variants linked instrumental variables in The inverse variance weighted method revealed 5 a ON, including order Erysipelotrichales (OR = 2.24, 95% CI 1.16-4.32, P .02), genus Christensenellaceae R 0.41, 0.19-0.87, family Erysipelotrichaceae Family XIII 0.45, 0.21-0.95, .04), class Erysipelotrichia .02). mitigated concerns regarding heterogeneity, directional pleiotropy, outliers (P > .05). However, showed no effect ON on these taxa. (single-nucleotide polymorphism) pinpointed 20 host genes pathogenesis. These findings lay groundwork microbiota-targeted therapies deepen our understanding gut-bone axis osteonecrosis.

Language: Английский

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Mitochondria derived from Stem cells modulated the biological behavior of monocyte-macrophages and inhibited inflammatory bone resorption

BMC Musculoskeletal Disorders, Journal Year: 2025, Volume and Issue: 26(1)

Published: March 22, 2025

The transfer of mitochondria from stem cells effectively attenuates the viability inflammatory cells. However, there is a paucity research supporting inhibitory effect on bone resorption through mitochondrial transfer. Mouse models were established to investigate impact cell-derived mitochondria. Stem cells, and exosomes injected into animal for experimental research. Healthy mice with included as control groups. calvaria evaluated by immunofluorescence, gross morphology, micro-computed tomography (micro-CT), immunohistochemical staining. Monocyte-macrophages incubated group. activated monocyte-macrophages cultured separately served biological behavior enzyme-linked immunosorbent assay (ELISA), Multiskan FC, histochemical successfully transferred monocyte-macrophages. In vivo, local injection mitochondria, mitigated cell infiltration, suppressed osteoclast maturation, demonstrated higher relative volume in mouse compared negative vitro, co-incubation secretion cytokines, proliferation, fusion, osteoclastogenesis modulation behaviors may occur thereby mitigating resorption.

Language: Английский

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Transferrin receptors

Experimental & Molecular Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

Language: Английский

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Hepcidin Deficiency Disrupts Iron Homeostasis and Induces Ferroptosis in Zebrafish Liver

Fishes, Journal Year: 2025, Volume and Issue: 10(5), P. 243 - 243

Published: May 21, 2025

Hepcidin is a key regulator of systemic iron homeostasis, which essential for maintaining balance and cellular health. To investigate its role in zebrafish, we empolyed hepcidin knockout model. Morphological histological analyses revealed pale livers significant accumulation hep−/− particularly liver, skin, egg tissues. RNA sequencing identified 1,424 differentially expressed genes (DEGs) between wild-type (WT) with enrichment pathways related to ferroptosis, fatty acid degradation, heme binding. Western blot analysis showed reduced levels iron-related proteins, including GPX4, Fth1, ferroportin (FPN), indicating impaired transport increased oxidative stress. Gene Ontology (GO) KEGG highlighted disruptions metabolism lipid oxidation, linking overload ferroptosis the absence hepcidin. These findings demonstrate that deficiency leads profound dysregulation driving peroxidation zebrafish liver. Our study provides mechanistic insights into molecular consequences loss, advancing our understanding damage physiological impacts.

Language: Английский

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Multinucleation resets human macrophages for specialized functions at the expense of their identity

EMBO Reports, Journal Year: 2023, Volume and Issue: 24(3)

Published: Jan. 4, 2023

Abstract Macrophages undergo plasma membrane fusion and cell multinucleation to form multinucleated giant cells (MGCs) such as osteoclasts in bone, Langhans (LGCs) part of granulomas or foreign‐body (FBGCs) reaction exogenous material. How per se contributes functional specialization mature mononuclear macrophages remains poorly understood humans. Here, we integrate comparative transcriptomics with assays purified human osteoclasts, LGCs FBGCs. Strikingly, all three types MGCs, causes a pronounced downregulation macrophage identity. We show enhanced lysosome‐mediated intracellular iron homeostasis promoting MGC formation. The transition from multinuclear state is accompanied by specific each polykaryon. Enhanced phagocytic mitochondrial function associate FBGCs respectively. Moreover, preferentially express B7‐H3 (CD276) can granuloma‐like clusters vitro , suggesting that their potentiates T activation. These findings demonstrate how cell–cell reset identity an advanced maturation step confers MGC‐specific functionality.

Language: Английский

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