PMAIP1, a novel diagnostic and potential therapeutic biomarker in osteoporosis
Tao Li1, Jinghong Yuan1,2, Peichuan Xu1
1Institute of Orthopaedics of Jiangxi Province, Nanchang, Jiangxi, China.
Background:
Osteoporosis is a common endocrine metabolic bone disease, which may lead to severe consequences. However, the unknown molecular mechanism of osteoporosis, the observable side effects of present treatments and the inability to fundamentally improve bone metabolism seriously restrict the impact of prevention and treatment. The study aims to identify potential biomarkers from osteoclast progenitors, specifically peripheral blood monocytes on predicting the osteoporotic phenotype.
Methods:
Datasets were obtained from Gene Expression Omnibus (GEO). Based on the differentially expressed genes (DEGs) and GSEA results, GO and KEGG analyses were performed using the DAVID database and Metascape database. PPI network, TF network, drug-gene interaction network, and ceRNA network were established to determine the hub genes. Its osteogenesis, migration, and proliferation abilities in bone marrow mesenchymal stem cells (BMSCs) were validated through RT-qPCR, WB, ALP staining, VK staining, wound healing assay, transwell assay, and CCK-8 assay.
Results:
A total of 63 significant DEGs were screened. Functional and pathway enrichment analysis discovered that the functions of the significant DEGs (SDEGs) are mainly related to immunity and metal ions. A comprehensive evaluation of all the network analyses, PMAIP1 was defined as osteoporosis's core gene. This conclusion was further confirmed in clinical cohort data. A series of experiments demonstrated that the PMAIP1 gene can promote the osteogenesis, migration and proliferation of BMSC cells.
Conclusions:
All of these outcomes showed a new theoretical basis for further research in the treatment of osteoporosis, and PMAIP1 was identified as a potential biomarker for osteoporosis diagnosis and treatment.
Insights
Researchers identified PMAIP1 as a key gene in osteoporosis by analyzing gene expression data. This discovery offers a new target for diagnosing and treating osteoporosis, potentially improving bone metabolism.
Area of Science:
- Endocrinology
- Metabolic Bone Diseases
- Molecular Biology
Background:
- Osteoporosis is a prevalent metabolic bone disease with unknown molecular mechanisms and limited treatment efficacy.
- Current osteoporosis treatments have side effects and do not fundamentally improve bone metabolism.
- Identifying novel biomarkers is crucial for effective osteoporosis prevention and treatment.
Purpose of the Study:
- To identify potential biomarkers from osteoclast progenitors for predicting osteoporosis.
- To elucidate the molecular mechanisms underlying osteoporosis.
- To discover new therapeutic targets for osteoporosis.
Main Methods:
- Differential gene expression analysis of peripheral blood monocytes.
- Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO), and KEGG pathway analysis.
- Construction of protein-protein interaction (PPI), transcription factor (TF), drug-gene, and ceRNA networks.
- In vitro validation of gene function in bone marrow mesenchymal stem cells (BMSCs) using assays like RT-qPCR, Western Blot, ALP staining, and CCK-8.
Main Results:
- 63 significant differentially expressed genes (DEGs) were identified, primarily related to immunity and metal ions.
- PMAIP1 was identified as a core gene associated with osteoporosis through network analyses and validated in clinical data.
- PMAIP1 was shown to promote osteogenesis, migration, and proliferation in BMSCs.
Conclusions:
- PMAIP1 is a potential biomarker for osteoporosis diagnosis and treatment.
- The study provides a new theoretical basis for osteoporosis research and therapeutic strategies.
- Targeting PMAIP1 may offer a novel approach to improve bone metabolism and treat osteoporosis.
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