CYP27A1 deficiency promoted osteoclast differentiation

Fang, Ziqi; Cheng, Guangdong; He, Mengting; Lin, Yen‐Ting

doi:10.7717/peerj.15041

Cited by 4 publications

(1 citation statement)

References 31 publications

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“…Disruption of neutrophil elastase function as a result of genetic alterations may lead to diminished bone density and an elevated risk of fractures. [18] Moreover, research suggests that AKT1 may play a role in the regulation of bone metabolism and density. Activation of the AKT1 pathway has been linked to enhanced bone formation and reduced bone resorption, which are crucial for preserving skeletal integrity.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis of key genes, immune infiltration, and risk assessment in low bone mineral density among perimenopausal women: An observational study

Chen,

2024

Medicine

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This study aimed to identify hub genes and elucidate the molecular mechanisms underlying low bone mineral density (BMD) in perimenopausal women. R software was used to normalize the dataset and screen the gene set associated with BMD in perimenopausal women from the Gene Expression Omnibus database. Cytoscape software was used to identify 7 critical genes. Gene enrichment analysis and protein interaction was employed to further analyze the core genes, and the CIBERSORT deconvolution algorithm was used to perform immune infiltration analysis of 22 immune genes in the samples. Furthermore, an analysis of the immune correlations of 7 crucial genes was conducted. Subsequently, a receiver operating characteristic curve was constructed to assess the diagnostic efficacy of these essential genes. A total of 171 differentially expressed genes were identified that were primarily implicated in the signaling pathways associated with apoptosis. Seven crucial genes (CAMP, MMP8, HMOX1, CTNNB1, ELANE, AKT1, and CEACAM8) were effectively filtered. The predominant functions of these genes were enriched in specific granules. The pivotal genes displayed robust associations with activated dendritic cells. The developed risk model showed a remarkable level of precision, as evidenced by an area under the curve of 0.8407 and C-index of 0.854. The present study successfully identified 7 crucial genes that are significantly associated with low BMD in perimenopausal women. Consequently, this research offers a solid theoretical foundation for clinical risk prediction, drug sensitivity analysis, and the development of targeted drugs specifically tailored for addressing low BMD in perimenopausal women.

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Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis of key genes, immune infiltration, and risk assessment in low bone mineral density among perimenopausal women: An observational study

Chen,

2024

Medicine

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Mechanism of NPC1L1 mediated 27-hydroxycholesterol metabolisms in the occurrence and development of osteoporosis

Li,

Lv,

Chen

et al. 2024

Preprint

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Cholesterol metabolism is closely related to the occurrence and development of osteoporosis, but the exact mechanism remains unclear. Niemann-Pick C1-like 1 (NPC1L1) is one of the key cholesterol transporter proteins, however, there are few reports on the functions of NPC1L1 besides regulating cholesterol transport, let alone bone homeostasis. Our preliminary research indicated that NPC1L1 may play a negative regulatory role in osteogenic differentiation. In this study, using in vitro osteogenic differentiation experiment and mouse osteoporosis model, we showed here that NPC1L1 expression was downregulated during osteogenesis, and NPC1L1 knockdown significantly enhanced osteogenic differentiation ability of osteoblasts and delayed progress of osteoporosis. Mechanistically, through RNA sequencing, NPC1L1 was found regulate cholesterol metabolism rather than transportation. It increased 27- Hydroxycholesterol (27-OHC) level through activating 27-hydroxylase (Cyp27a1), resulting in 27-OHC accumulation in osteoblasts and inhibition of osteogenesis. Moreover, C/EBPα was proved mediated NPC1L1 promotes production of 27-OHC by Cyp27a1. These findings reveal that NPC1L1 inhibits osteogenesis and promotes osteoporosis via regulate cholesterol metabolism.

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Multi‐omics Analysis to Identify Key Immune Genes for Osteoporosis based on Machine Learning and Single‐cell Analysis

Zhang,

Pei,

Tian

et al. 2024

Orthopaedic Surgery

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ObjectiveOsteoporosis is a severe bone disease with a complex pathogenesis involving various immune processes. With the in‐depth understanding of bone immune mechanisms, discovering new therapeutic targets is crucial for the prevention and treatment of osteoporosis. This study aims to explore novel bone immune markers related to osteoporosis based on single‐cell and transcriptome data, utilizing bioinformatics and machine learning methods, in order to provide novel strategies for the diagnosis and treatment of the disease.MethodsSingle cell and transcriptome data sets were acquired from Gene Expression Omnibus (GEO). The data was then subjected to cell communication analysis, pseudotime analysis, and high dimensional WGCNA (hdWGCNA) analysis to identify key immune cell subpopulations and module genes. Subsequently, ConsensusClusterPlus analysis was performed on the key module genes to identify different diseased subgroups in the osteoporosis (OP) training set samples. The immune characteristics between subgroups were evaluated using Cibersort, EPIC, and MCP counter algorithms. OP's hub genes were screened using 10 machine learning algorithms and 113 algorithm combinations. The relationship between hub genes and immunity and pathways was established by evaluating the immune and pathway scores of the training set samples through the ESTIMATE, MCP‐counter, and ssGSEA algorithms. Real‐time fluorescence quantitative PCR (RT‐qPCR) testing was conducted on serum samples collected from osteoporosis patients and healthy adults.ResultsIn OP samples, the proportions of bone marrow‐derived mesenchymal stem cells (BM‐MSCs) and neutrophils increased significantly by 6.73% (from 24.01% to 30.74%) and 6.36% (from 26.82% to 33.18%), respectively. We found 16 intersection genes and four hub genes (DND1, HIRA, SH3GLB2, and F7). RT‐qPCR results showed reduced expression levels of DND1, HIRA, and SH3GLB2 in clinical blood samples of OP patients. Moreover, the four hub genes showed positive correlations with neutrophils (0.65–0.90), immature B cells (0.76–0.92), and endothelial cells (0.79–0.87), while showing negative correlations with myeloid‐derived suppressor cells (negative 0.54–0.73), T follicular helper cells (negative 0.71–0.86), and natural killer T cells (negative 0.75–0.85).ConclusionNeutrophils play a crucial role in the occurrence and development of osteoporosis. The four hub genes potentially inhibit metabolic activities and trigger inflammation by interacting with other immune cells, thereby significantly contributing to the onset and diagnosis of OP.

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CYP27A1 deficiency promoted osteoclast differentiation

Cited by 4 publications

References 31 publications

Bioinformatics analysis of key genes, immune infiltration, and risk assessment in low bone mineral density among perimenopausal women: An observational study

Bioinformatics analysis of key genes, immune infiltration, and risk assessment in low bone mineral density among perimenopausal women: An observational study

Mechanism of NPC1L1 mediated 27-hydroxycholesterol metabolisms in the occurrence and development of osteoporosis

Multi‐omics Analysis to Identify Key Immune Genes for Osteoporosis based on Machine Learning and Single‐cell Analysis

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