Based on multi-omics, revealing the key role of MOESIN lactic acidification-driven TGF-β signaling axis in improving diabetic osteoporosis through gut microbiota
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus Musculus
SUBMITTER: 
Jiajia Lu
PROVIDER: PXD076650 | iProX | Fri Apr 03 00:00:00 BST 2026
REPOSITORIES: iProX
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Project description:Background: Osteoporosis and diabetes represent major global public health challenges. Neutrophil extracellular traps (NETs) serve as key components of the innate immune system by capturing bacteria, fungi, and parasites, thereby trapping them in local environments with high concentrations of antimicrobial agents leading to their elimination. This study aimed to identify biomarkers associated with NETs in osteoporosis with diabetes, and to explore the underlying molecular mechanisms. Methods: A transcriptomic sequencing dataset was obtained for osteoporosis combined with diabetes. The NETs-related genes (NETs-RGs) were obtained from previous literature. Biomarkers were identified through differential analysis, machine learning, and receiver operating characteristic (ROC). The identified biomarkers were further validated by qRT-PCR and ELISA. Subsequently, molecular regulatory network construction, immune infiltration analysis, enrichment analysis, and drug prediction were conducted. Results: S100A12 and SLC25A37 were identified as biomarkers. Their significant upregulation at the protein level was further confirmed by experimental validation in an independent cohort. Enrichment analysis indicated that S100A12 was significantly enriched in 68 pathways, including \"ECM receptor interaction\", \"maturity onset diabetes of the young\", and others. SLC25A37 was significantly enriched in 54 pathways, primarily including \"ribosome\", \"leishmania infection\", and \"Toll-like receptor signaling pathway\". A total of 7 immune cell types exhibited significant differences between the two groups, including neutrophils and regulatory T cells. A total of 59 miRNAs and 43 lncRNAs were predicted. Additionally, XIST-hsa-miR-146a-5p-S100A12 and XIST-hsa-miR-7-5-SLC25A37 were suggested to have potential regulatory roles in osteoporosis with diabetes. Drugs such as rimegepant and eptinezumab were associated with biomarkers. Conclusion: S100A12 and SLC25A37 were identified as biomarkers associated with NETs in osteoporosis with diabetes, providing a theoretical foundation for developing targeted treatments for osteoporosis with diabetes.
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Project description:Recent studies have shown that microRNAs (miRNAs) are implicated in the development of postmenopausal osteoporosis, implying potential biomarkers. We performed a microarray-based expression scanning to search for potential circulating miRNA biomarkers for postmenopausal osteoporosis as whole blood obtianed from patients was used. MiRNA expression in the whole blood of 23 Chinese postmenopausal women with osteopenia and that of 25 Chinese postmenopausal women with osteoporosis. After total RNA was extracted, all of the RNA extraction samples were seperately pooled into six subgroups according to the T-score measurement.
2014-12-23 | E-GEOD-64433 | biostudies-arrayexpress
Project description:Osteoporosis represents a significant health challenge, particularly in postmenopausal women. While traditional medicine offers potential solutions, the mechanisms underlying their efficacy remain elusive. This study demonstrates the bone-protective properties of Guilu Erxian gel decoction (GEX), a traditional medicine prepared from tortoise plastron, antler, and herbs, by elucidating its impact on gut microbiota and associated metabolites. Using an ovariectomized mouse model of postmenopausal osteoporosis, we demonstrate that GEX consumption significantly reduces key osteoporotic markers, including low bone mineral density, compromised trabecular microstructure, and reduced biomechanical strength. GEX intake profoundly reshapes the gut microbiome, enriching beneficial bacteria crucial for fatty acid metabolism and mineral absorption. Gut microbiota transplantation from GEX-fed mice to ovariectomized recipients reversed probiotic bacterial abundance, particularly Bifidobacterium and Akkermansia. This intervention effectively alleviated ovariectomy-induced colon inflammation, trimethylamine N-oxide (TMAO) overproduction, and osteoporosis progression. Excessive TMAO promotes osteoclastogenic differentiation in macrophages in vitro. Using μCT imaging, biomechanical testing, histological staining, and 16S rRNA sequencing, we provide compelling evidence for the complex therapeutic effects of GEX, including mitigation of osteoclast overburden, reduction of marrow adiposis, suppression of RANKL overproduction, and preservation of colon goblet cell mucin. This study demonstrates the interplay between gut microbiota, its metabolite TMAO, and bone health, offering new insights into the mechanism of action of GEX. Our findings not only validate the bone-protective potential of this traditional medicine but also open new avenues for developing microbiome-based strategies to combat osteoporosis.
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Project description:In the present study we analyzed the effect of primary osteoporosis on the transcriptome of human mesenchymal stem cells (hMSC; alternatively named mesenchymal stromal cells) from human bone marrow. Human MSC of elderly patients suffering from osteoporosis were isolated from femoral heads after low-energy fracture of the femoral neck. Bone marrow of age-matched, non-osteoporotic donors was obtained of femoral heads after total hip arthroplasty. Cells were isolated from human bone marrow according to the previously described protocol (Noth et al., 2002, J Orthop Res, 20/5, 1060-1069) under agreement of the local Ethics Committee of the University of Würzburg. Human MSC of elderly patients suffering from osteoporosis were isolated from femoral heads after low-energy fracture of the femoral neck. Additional criteria for confirming primary osteoporosis in these donors were vertebrae fractures and advanced age. Bone marrow of age-matched, non-osteoporotic donors was obtained of femoral heads after total hip arthroplasty due to osteoarthritis and/or hip dysplasia. RNA samples were taken from passage 1 or passage 2.
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Project description:Background: Osteoporosis is one of the most common chronic diseases around the world, especially in postmenopausal women. Circular RNAs (circRNAs) are emerging as important regulators in human disease. The aim of the present study was to analyze circRNA expression profiles in osteoporosis and to explore the clinical significance. Methods: The serum samples were collected from osteoporosis patients and healthy people. The circRNA array was performed to screen for differentially expressed circRNAs. The mRNA expression levels of target genes were analyzed by quantitative real-time PCR (qRT-PCR). Results: Hsa_circ_0006859 was identified as one of the most upregulated circRNAs in the microarray analysis. Hsa_circ_0006859 in exosome was upregulated in osteoporosis patients compared with healthy controls. Hsa_circ_0006859 could differentiate osteopenia or osteoporosis patients from healthy controls with high sensitivity and specificity. Conclusion: Exosomal hsa_circ_0006859 is a potential biomarker for postmenopausal osteoporosis.
2020-11-13 | GSE161361 | GEO
Project description:<p>Backround&Aim: Dysbiosis of gut microbiota is closely related to the pathogenesis of osteoporosis (OP). This study aimed to identify probiotic candidates and gut-derived metabolites capable of ameliorating osteoporosis via modulation of bone metabolism. </p><p>Methods: Ovariectomized (OVX) rats were used to model PMOP. Multi-omics analyses, including 16S rDNA sequencing, metagenomics, and untargeted metabolomics, were conducted to characterize gut microbiota(GM) and metabolic alterations following icariin (ICA) administration. Probiotic candidates enriched by ICA treatment were screened based on microbial and metabolic profiles. The effects of P. distasonis (LPD) were evaluated via oral gavage and fecal microbiota transplantation (FMT) in pseudo-germ-free OVX rats. Fecal samples from PMOP patients were analyzed using qPCR to assess LPD abundance. In vitro assays were performed to examine the osteogenic and anti-resorptive activities of glycerophospholipid metabolites derived from LPD.</p><p>Results: ICA administration improved bone microarchitecture and mechanical strength in OVX rats, restored intestinal barrier integrity, and altered GM composition. Multi-omics analysis identified Parabacteroides distasonis as a key bacterium enriched by ICA. Oral gavage of LPD and FMT from ICA-treated donors ameliorated bone loss in pseudo-germ-free OVX rats. Quantitative PCR of fecal samples confirmed reduced LPD abundance in PMOP patients. Metabolomic profiling revealed that ICA and LPD elevated circulating levels of phosphatidylcholine (PC), lysophosphatidylethanolamine (Lyso PE), and lysophosphatidylcholine (Lyso PC), which were positively correlated with bone formation markers. In vitro, these metabolites enhanced osteoblast differentiation and suppressed osteoclastogenesis.</p><p><strong>Conclusions: </strong>ICA exerts anti-osteoporotic effects via GM modulation, in part through enrichment of LPD and its glycerophospholipid metabolites. These findings highlight LPD as a promising probiotic candidate and support the therapeutic potential of targeting the gut-bone axis in PMOP.</p><p><br></p>
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