{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T06:11:43Z","timestamp":1777356703079,"version":"3.51.4"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T00:00:00Z","timestamp":1721952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Prior research has demonstrated that programmed cell death (PCD) and mitochondria assume pivotal roles in controlling cellular metabolism and maintaining bone cell equilibrium. Nonetheless, the comprehensive elucidation of their mode of operation in osteoporosis (OP) warrants further investigation. Therefore, this study aimed at analyzing the role of genes associated with PCD (PCD-RGs) and mitochondria (mortality factor-related genes; MRGs) in OP.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Differentially expressed genes (DEGs) were identified by subjecting the GSE56815 dataset obtained from the Gene Expression Omnibus database to differential expression analysis and comparing OP patients with healthy individuals. The genes of interest were ascertained through the intersection of DEGs, MRGs, and PCD-RGs; these genes were filtered using machine learning methodologies to discover potential biomarkers. The prospective biomarkers displaying uniform patterns and statistically meaningful variances were identified by evaluating their levels in the GSE56815 dataset and conducting quantitative real-time polymerase chain reaction-based assessments. Moreover, the functional mechanisms of these biomarkers were further delineated by constructing a nomogram, which conducted gene set enrichment analysis, explored immune infiltration, generated regulatory networks, predicted drug responses, and performed molecular docking analyses.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Eighteen candidate genes were documented contingent upon the intersection between 2,354 DEGs, 1,136 MRGs, and 1,548 PCD-RGs. The biomarkers <jats:italic>DAP3<\/jats:italic>, <jats:italic>BIK<\/jats:italic>, and <jats:italic>ACAA2<\/jats:italic> were upregulated in OP and were linked to oxidative phosphorylation. Furthermore, the predictive ability of the nomogram designed based on the OP biomarkers exhibited a certain degree of accuracy. Correlation analysis revealed a strong positive correlation between CD56dim natural killer cells and <jats:italic>ACAA2<\/jats:italic> and a significant negative correlation between central memory CD4<jats:sup>+<\/jats:sup> T cells and <jats:italic>DAP3<\/jats:italic>. <jats:italic>DAP3<\/jats:italic>, <jats:italic>BIK<\/jats:italic>, and <jats:italic>ACAA2<\/jats:italic> were regulated by multiple factors; specifically, SETDB1 and ZNF281 modulated <jats:italic>ACAA2<\/jats:italic> and <jats:italic>DAP3<\/jats:italic>, whereas TP63 and TFAP2C governed <jats:italic>DAP3<\/jats:italic> and <jats:italic>BIK<\/jats:italic>. Additionally, a stable binding force was observed between the drugs (estradiol, valproic acid, and CGP52608) and the biomarkers.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> This investigation evidenced that the biomarkers <jats:italic>DAP3<\/jats:italic>, <jats:italic>BIK<\/jats:italic>, and <jats:italic>ACAA2<\/jats:italic> are associated with PCD and mitochondria in OP, potentially facilitate the diagnosis of OP in clinical settings.<\/jats:p>","DOI":"10.3389\/fgene.2024.1439171","type":"journal-article","created":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T04:37:47Z","timestamp":1721968667000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Identification and experimental validation of programmed cell death- and mitochondria-associated biomarkers in osteoporosis and immune microenvironment"],"prefix":"10.3389","volume":"15","author":[{"given":"Xiu","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheng-Chao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun-Nan","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han-Lin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong-Shen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing-Quan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin-Shui","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wu-Bing","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,7,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"14583","DOI":"10.3390\/ijms241914583","article-title":"Osteoporosis: molecular pathology, diagnostics, and therapeutics","volume":"24","author":"Adejuyigbe","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1002\/JLB.MR0718-299R","article-title":"Senescent cells: living or dying is a matter of NK cells","volume":"105","author":"Antonangeli","year":"2019","journal-title":"J. Leukoc. Biol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"e32499","DOI":"10.1097\/MD.0000000000032499","article-title":"Exploring the regulatory mechanism of osteoporosis based on intestinal flora: a review","volume":"101","author":"Awuti","year":"2022","journal-title":"Med. (Baltim)"},{"key":"B4","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1038\/s41580-020-0270-8","article-title":"Emerging connectivity of programmed cell death pathways and its physiological implications","volume":"21","author":"Bedoui","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"2182","DOI":"10.3389\/fimmu.2019.02182","article-title":"Chemokines in physiological and pathological bone remodeling","volume":"10","author":"Brylka","year":"2019","journal-title":"Front. Immunol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"4101738","DOI":"10.1155\/2019\/4101738","article-title":"AKT-GSK3\u03b2 signaling pathway regulates mitochondrial dysfunction-associated OPA1 cleavage contributing to osteoblast apoptosis: preventative effects of hydroxytyrosol","volume":"2019","author":"Cai","year":"2019","journal-title":"Oxid. Med. Cell Longev."},{"key":"B7","doi-asserted-by":"publisher","first-page":"e95083","DOI":"10.7554\/eLife.95083","article-title":"Current perspectives on the multiple roles of osteoclasts: mechanisms of osteoclast-osteoblast communication and potential clinical implications","volume":"13","author":"Daponte","year":"2024","journal-title":"eLife"},{"key":"B8","doi-asserted-by":"publisher","first-page":"ITC1","DOI":"10.7326\/AITC202401160","article-title":"Osteoporosis","volume":"177","author":"Ensrud","year":"2024","journal-title":"Ann. Intern Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.semcdb.2021.05.014","article-title":"Interaction between bone and immune cells: implications for postmenopausal osteoporosis","volume":"123","author":"Fischer","year":"2022","journal-title":"Semin. Cell Dev. Biol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e79725","DOI":"10.7554\/elife.79725","article-title":"Regulation of defective mitochondrial DNA accumulation and transmission in C. elegans by the programmed cell death and aging pathways","volume":"12","author":"Flowers","year":"2023","journal-title":"Elife"},{"key":"B11","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1186\/s12916-017-0786-8","article-title":"Osteoprotegerin and breast cancer risk by hormone receptor subtype: a nested case-control study in the EPIC cohort","volume":"15","author":"Fortner","year":"2017","journal-title":"BMC Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1669","DOI":"10.1007\/s00210-023-02484-8","article-title":"The 10th International Conference on cGMP 2022: recent trends in cGMP research and development-meeting report","volume":"396","author":"Friebe","year":"2023","journal-title":"Naunyn Schmiedebergs Arch Pharmacol. The 10th Int. Conf. cGMP"},{"key":"B13","doi-asserted-by":"publisher","first-page":"706907","DOI":"10.3389\/fgene.2021.706907","article-title":"ggVennDiagram: an intuitive, easy-to-use, and highly customizable R package to generate venn diagram","volume":"12","author":"Gao","year":"2021","journal-title":"Front. Genet."},{"key":"B14","doi-asserted-by":"publisher","first-page":"2315","DOI":"10.1007\/s12015-022-10370-8","article-title":"Telomeres and mitochondrial metabolism: implications for cellular senescence and age-related diseases","volume":"18","author":"Gao","year":"2022","journal-title":"Stem Cell Rev. Rep."},{"key":"B15","doi-asserted-by":"publisher","first-page":"2847","DOI":"10.1093\/bioinformatics\/btw313","article-title":"Complex heatmaps reveal patterns and correlations in multidimensional genomic data","volume":"32","author":"Gu","year":"2016","journal-title":"Bioinformatics"},{"key":"B16","doi-asserted-by":"publisher","first-page":"319","DOI":"10.3892\/ijmm.2016.2606","article-title":"IL-1\u03b1 induces apoptosis and inhibits the osteoblast differentiation of MC3T3-E1 cells through the JNK and p38 MAPK pathways","volume":"38","author":"Guo","year":"2016","journal-title":"Int. J. Mol. Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"3844","DOI":"10.1093\/bioinformatics\/btac409","article-title":"Ggtranscript: an R package for the visualization and interpretation of transcript isoforms using ggplot2","volume":"38","author":"Gustavsson","year":"2022","journal-title":"Bioinformatics"},{"key":"B18","doi-asserted-by":"publisher","first-page":"633295","DOI":"10.3389\/fgene.2021.633295","article-title":"Identification of miRNA in sheep intramuscular fat and the role of miR-193a-5p in proliferation and differentiation of 3T3-L1","volume":"12","author":"Han","year":"2021","journal-title":"Front. Genet."},{"key":"B19","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/1471-2105-14-7","article-title":"GSVA: gene set variation analysis for microarray and RNA-seq data","volume":"14","author":"H\u00e4nzelmann","year":"2013","journal-title":"BMC Bioinforma."},{"key":"B20","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1515\/bmc-2016-0015","article-title":"Bcl-2 family proteins: Master regulators of cell survival","volume":"7","author":"Hatok","year":"2016","journal-title":"Biomol. Concepts"},{"key":"B21","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1007\/164_2016_117","article-title":"Role of mitochondrial reactive oxygen species in the activation of cellular signals, molecules, and function","volume":"240","author":"Indo","year":"2017","journal-title":"Handb. Exp. Pharmacol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"109676","DOI":"10.1016\/j.biopha.2019.109676","article-title":"Cytoprotective effect of Fufang Lurong Jiangu capsule against hydrogen peroxide-induced oxidative stress in bone marrow stromal cell-derived osteoblasts through the Nrf2\/HO-1 signaling pathway","volume":"121","author":"Jin","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"B23","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1038\/cdd.2017.186","article-title":"BCL-2 family proteins: changing partners in the dance towards death","volume":"25","author":"Kale","year":"2018","journal-title":"Cell Death Differ."},{"key":"B24","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1111\/nyas.14486","article-title":"The NO-cGMP-PKG pathway in skeletal remodeling","volume":"1487","author":"Kim","year":"2021","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"B25","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1007\/s11914-023-00825-3","article-title":"Novel Insights into osteoclast energy metabolism","volume":"21","author":"Ledesma-Colunga","year":"2023","journal-title":"Curr. Osteoporos. Rep."},{"key":"B26","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1038\/s41419-023-05595-5","article-title":"PINK1\/Parkin-mediated mitophagy inhibits osteoblast apoptosis induced by advanced oxidation protein products","volume":"14","author":"Li","year":"","journal-title":"Cell Death Dis."},{"key":"B27","doi-asserted-by":"publisher","first-page":"106635","DOI":"10.1016\/j.phrs.2022.106635","article-title":"Cell death regulation: a new way for natural products to treat osteoporosis","volume":"187","author":"Li","year":"","journal-title":"Pharmacol. Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1325317","DOI":"10.3389\/fendo.2024.1325317","article-title":"Mitochondrial dysfunction and therapeutic perspectives in osteoporosis","volume":"15","author":"Liu","year":"2024","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"B29","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"B30","doi-asserted-by":"publisher","first-page":"e230116","DOI":"10.1530\/JOE-23-0116","article-title":"Postmenopausal osteoporosis coexisting with sarcopenia: the role and mechanisms of estrogen","volume":"259","author":"Lu","year":"2023","journal-title":"J. Endocrinol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1038\/nrm2239","article-title":"Self-eating and self-killing: crosstalk between autophagy and apoptosis","volume":"8","author":"Maiuri","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"D132","DOI":"10.1093\/nar\/gkt976","article-title":"SMMRNA: a database of small molecule modulators of RNA","volume":"42","author":"Mehta","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"B33","doi-asserted-by":"publisher","first-page":"114403","DOI":"10.1016\/j.biopha.2023.114403","article-title":"Suppression of apoptosis in osteocytes, the potential way of natural medicine in the treatment of osteonecrosis of the femoral head","volume":"162","author":"Meng","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"B34","doi-asserted-by":"publisher","first-page":"2785","DOI":"10.1002\/jcc.21256","article-title":"AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility","volume":"30","author":"Morris","year":"2009","journal-title":"J. Comput. Chem."},{"key":"B35","doi-asserted-by":"publisher","first-page":"116675","DOI":"10.1016\/j.bone.2023.116675","article-title":"Effect of T cells on bone","volume":"168","author":"Okamoto","year":"2023","journal-title":"Bone"},{"key":"B36","doi-asserted-by":"publisher","first-page":"115305","DOI":"10.1016\/j.bone.2020.115305","article-title":"Skeletal restoration by phosphodiesterase 5 inhibitors in osteopenic mice: evidence of osteoanabolic and osteoangiogenic effects of the drugs","volume":"135","author":"Pal","year":"2020","journal-title":"Bone"},{"key":"B37","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1186\/s12967-023-04468-x","article-title":"Integrated machine learning survival framework develops a prognostic model based on inter-crosstalk definition of mitochondrial function and cell death patterns in a large multicenter cohort for lower-grade glioma","volume":"21","author":"Qin","year":"2023","journal-title":"J. Transl. Med."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1698","DOI":"10.7150\/thno.30640","article-title":"Berberine protects glomerular podocytes via inhibiting drp1-mediated mitochondrial fission and dysfunction","volume":"9","author":"Qin","year":"2019","journal-title":"Theranostics"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1080","DOI":"10.1016\/S0140-6736(21)02646-5","article-title":"Drug therapy for osteoporosis in older adults","volume":"399","author":"Reid","year":"2022","journal-title":"Lancet"},{"key":"B40","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"Limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"B41","doi-asserted-by":"publisher","first-page":"11371","DOI":"10.1038\/s41598-022-15054-4","article-title":"Caging and photo-triggered uncaging of singlet oxygen by excited state engineering of electron donor-acceptor-linked molecular sensors","volume":"12","author":"Sasikumar","year":"2022","journal-title":"Sci. Rep."},{"key":"B42","doi-asserted-by":"publisher","first-page":"687037","DOI":"10.3389\/fimmu.2021.687037","article-title":"Immunoporosis: role of innate immune cells in osteoporosis","volume":"12","author":"Saxena","year":"2021","journal-title":"Front. Immunol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1007\/s10822-010-9352-6","article-title":"Ligand docking and binding site analysis with PyMOL and Autodock\/Vina","volume":"24","author":"Seeliger","year":"2010","journal-title":"J. Comput. Aided Mol. Des."},{"key":"B44","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: a software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"B45","doi-asserted-by":"publisher","first-page":"16019","DOI":"10.1074\/jbc.RA118.004102","article-title":"Active mitochondria support osteogenic differentiation by stimulating \u03b2-catenin acetylation","volume":"293","author":"Shares","year":"2018","journal-title":"J. Biol. Chem."},{"key":"B46","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.ceb.2017.12.010","article-title":"Mitochondrial regulation of hematopoietic stem cells","volume":"49","author":"Snoeck","year":"2017","journal-title":"Curr. Opin. Cell Biol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1323751","DOI":"10.3389\/fonc.2023.1323751","article-title":"Death-associated protein 3 in cancer-discrepant roles of DAP3 in tumours and molecular mechanisms","volume":"13","author":"Song","year":"2023","journal-title":"Front. Oncol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1038\/s41556-018-0124-1","article-title":"The multifaceted contributions of mitochondria to cellular metabolism","volume":"20","author":"Spinelli","year":"2018","journal-title":"Nat. Cell Biol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1831","DOI":"10.1007\/s40265-021-01625-8","article-title":"The effects of osteoporotic and non-osteoporotic medications on fracture risk and bone mineral density","volume":"81","author":"van der Burgh","year":"2021","journal-title":"Drugs"},{"key":"B51","doi-asserted-by":"publisher","first-page":"557","DOI":"10.3389\/fendo.2019.00557","article-title":"Estrogens, estrogen receptors effects on cardiac and skeletal muscle mitochondria","volume":"10","author":"Ventura-Clapier","year":"2019","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"B52","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1530\/eje.1.02217","article-title":"The ACAA-insertion\/deletion polymorphism at the 3\u2032 UTR of the IGF-II receptor gene is associated with type 2 diabetes and surrogate markers of insulin resistance","volume":"155","author":"Villuendas","year":"2006","journal-title":"Eur. J. Endocrinol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1979","DOI":"10.1056\/NEJMcp2307353","article-title":"Postmenopausal osteoporosis","volume":"389","author":"Walker","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"B54","doi-asserted-by":"publisher","first-page":"1394","DOI":"10.3390\/antiox10091394","article-title":"Biophysical modulation of the mitochondrial metabolism and redox in bone homeostasis and osteoporosis: how biophysics converts into bioenergetics","volume":"10","author":"Wang","year":"2021","journal-title":"Antioxidants (Basel)"},{"key":"B55","doi-asserted-by":"publisher","first-page":"8091","DOI":"10.26355\/eurrev_201812_16499","article-title":"Mitochondrial protein OPA mediates osteoporosis induced by radiation through the P38 signaling pathway","volume":"22","author":"Wang","year":"2018","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"B56","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.cell.2011.11.030","article-title":"The mitochondrial phosphatase PGAM5 functions at the convergence point of multiple necrotic death pathways","volume":"148","author":"Wang","year":"2012","journal-title":"Cell"},{"key":"B57","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/s12935-015-0187-z","article-title":"The role of death-associated protein 3 in apoptosis, anoikis and human cancer","volume":"15","author":"Wazir","year":"2015","journal-title":"Cancer Cell Int."},{"key":"B58","doi-asserted-by":"publisher","first-page":"100141","DOI":"10.1016\/j.xinn.2021.100141","article-title":"clusterProfiler 4.0: a universal enrichment tool for interpreting omics data","volume":"2","author":"Wu","year":"2021","journal-title":"Innovation (Camb)"},{"key":"B59","doi-asserted-by":"publisher","first-page":"e21147","DOI":"10.1016\/j.heliyon.2023.e21147","article-title":"A nomogram for predicting prognosis of patients with cervical cerclage","volume":"9","author":"Xu","year":"2023","journal-title":"Heliyon"},{"key":"B60","doi-asserted-by":"publisher","first-page":"2123","DOI":"10.1002\/tox.23327","article-title":"Overexpression of HIF-1\u03b1 enhances the protective effect of mitophagy on steroid-induced osteocytes apoptosis","volume":"36","author":"Xu","year":"2021","journal-title":"Environ. Toxicol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"990888","DOI":"10.3389\/fgene.2022.990888","article-title":"Bioinformatics analysis to screen for genes related to myocardial infarction","volume":"13","author":"Yang","year":"2022","journal-title":"Front. Genet."},{"key":"B62","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1111\/prd.12422","article-title":"Osteoporosis and periodontal diseases \u2013 an update on their association and mechanistic links","volume":"89","author":"Yu","year":"2000","journal-title":"Periodontol"},{"key":"B63","doi-asserted-by":"publisher","first-page":"1182363","DOI":"10.3389\/fgene.2023.1182363","article-title":"Therapeutic approach of natural products that treat osteoporosis by targeting epigenetic modulation","volume":"14","author":"Zhang","year":"2023","journal-title":"Front. Genet."},{"key":"B64","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1186\/1471-2105-14-244","article-title":"RCircos: an R package for Circos 2D track plots","volume":"14","author":"Zhang","year":"2013","journal-title":"BMC Bioinforma."},{"key":"B65","doi-asserted-by":"publisher","first-page":"9281481","DOI":"10.1155\/2019\/9281481","article-title":"Curculigoside protects against excess-iron-induced bone loss by attenuating Akt-FoxO1-dependent oxidative damage to mice and osteoblastic MC3T3-E1 cells","volume":"2019","author":"Zhang","year":"2019","journal-title":"Oxid. Med. Cell Longev."},{"key":"B66","doi-asserted-by":"publisher","first-page":"2531","DOI":"10.1007\/s10528-023-10390-0","article-title":"Exploration of the shared hub genes and biological mechanism in osteoporosis and type 2 diabetes mellitus based on machine learning","volume":"61","author":"Zhao","year":"2023","journal-title":"Biochem. Genet."},{"key":"B67","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.molmed.2019.04.008","article-title":"Mitochondrial regulation of stem cells in bone homeostasis","volume":"26","author":"Zheng","year":"2020","journal-title":"Trends Mol. Med."},{"key":"B68","doi-asserted-by":"publisher","first-page":"3433","DOI":"10.3892\/ijmm.2018.3534","article-title":"Valproic acid prevents glucocorticoid-induced osteonecrosis of the femoral head of rats","volume":"41","author":"Zhou","year":"2018","journal-title":"Int. J. Mol. Med."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2024.1439171\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T04:37:52Z","timestamp":1721968672000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2024.1439171\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,26]]},"references-count":68,"alternative-id":["10.3389\/fgene.2024.1439171"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2024.1439171","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,26]]},"article-number":"1439171"}}