{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T08:26:39Z","timestamp":1786955199320,"version":"build-2736575974"},"reference-count":105,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"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. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Osteonecrosis of the femoral head (ONFH) is a progressive and disabling orthopedic disorder characterized by impaired bone remodeling and microvascular dysfunction. Emerging evidence identifies post-translational modifications (PTMs) as critical molecular switches linking external pathogenic stimuli, such as glucocorticoids and alcohol, to intracellular signaling dysregulation in ONFH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main Body<\/jats:title>\n                    <jats:p>This review comprehensively summarizes the regulatory roles of major PTMs-including phosphorylation, acetylation, methylation, and ubiquitination-in key cell types governing femoral head homeostasis, namely, bone marrow-derived mesenchymal stem cells, osteoblasts, osteocytes, osteoclasts, and vascular endothelial cells. Aberrant PTMs disrupt the osteogenic-adipogenic balance, impair angiogenesis, and trigger multiple forms of programmed cell death, including apoptosis and ferroptosis, collectively driving the pathological progression towards bone necrosis. Particular emphasis is placed on phosphorylation-dependent signaling pathways (e.g., PI3K\/Akt, GSK-3\u03b2\/\u03b2 -catenin, JAK2\/STAT3, and AMPK\/mTOR), ubiquitin-mediated mitochondrial quality control, and acetylation-driven epigenetic regulation. Furthermore, we highlight emerging PTM-targeted small-molecule interventions that show promise in restoring osteogenesis, preserving endothelial function, or suppressing cell death.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Future research directions include decoding cell type-specific \u201cPTM codes\u201d, integrating multi-omics analyses, and developing patient-derived organoid models. Advancing these areas may collectively enable earlier diagnosis and more precise, mechanism-based therapies for ONFH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1885721","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T08:12:42Z","timestamp":1786954362000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The role of post-translational modifications in osteonecrosis of the femoral head"],"prefix":"10.3389","volume":"14","author":[{"given":"Longxin","family":"An","sequence":"first","affiliation":[{"name":"Department of Trauma Orthopedics, Weifang People\u2019s Hospital, Shandong Second Medical University","place":["Weifang, China"]},{"name":"School of Clinical Medicine, Shandong Second Medical University","place":["Weifang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lizhi","family":"Cao","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, Shandong Second Medical University","place":["Weifang, China"]},{"name":"Department of Neurology, Weifang People\u2019s Hospital, Shandong Second Medical University","place":["Weifang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Trauma Orthopedics, Weifang People\u2019s Hospital, Shandong Second Medical University","place":["Weifang, China"]},{"name":"School of Clinical Medicine, Shandong Second Medical University","place":["Weifang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoming","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Trauma Orthopedics, Weifang People\u2019s Hospital, Shandong Second Medical University","place":["Weifang, China"]},{"name":"School of Clinical Medicine, Shandong Second Medical University","place":["Weifang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyong","family":"Ma","sequence":"additional","affiliation":[{"name":"Yanbian University Hospital, Yanbian University","place":["Yanji, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongzheng","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Trauma Orthopedics, Weifang People\u2019s Hospital, Shandong Second Medical University","place":["Weifang, China"]},{"name":"School of Clinical Medicine, Shandong Second Medical University","place":["Weifang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zilong","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Trauma Orthopedics, Weifang People\u2019s Hospital, Shandong Second Medical University","place":["Weifang, China"]},{"name":"School of Clinical Medicine, Shandong Second Medical University","place":["Weifang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Trauma Orthopedics, Weifang People\u2019s Hospital, Shandong Second Medical University","place":["Weifang, China"]},{"name":"School of Clinical Medicine, Shandong Second Medical University","place":["Weifang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naibo","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Trauma Orthopedics, Weifang People\u2019s Hospital, Shandong Second Medical University","place":["Weifang, China"]},{"name":"School of Clinical Medicine, Shandong Second Medical University","place":["Weifang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuecheng","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Trauma Orthopedics, Weifang People\u2019s Hospital, Shandong Second Medical University","place":["Weifang, China"]},{"name":"School of Clinical Medicine, Shandong Second Medical University","place":["Weifang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.1021\/acs.chemrev.7b00181","article-title":"Lysine acetylation goes global: from epigenetics to metabolism and therapeutics","volume":"118","author":"Ali","year":"2018","journal-title":"Chem. Rev."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3390\/ph11040107","article-title":"Influence of iron on bone homeostasis","volume":"11","author":"Balogh","year":"2018","journal-title":"Pharm. Basel, Switz."},{"key":"B3","doi-asserted-by":"publisher","first-page":"31065","DOI":"10.18632\/oncotarget.16075","article-title":"Novel akt activator SC-79 is a potential treatment for alcohol-induced osteonecrosis of the femoral head","volume":"8","author":"Chen","year":"2017","journal-title":"Oncotarget"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.7150\/ijbs.40917","article-title":"Steroid-induced osteonecrosis of the femoral head reveals enhanced reactive oxygen species and hyperactive osteoclasts","volume":"16","author":"Chen","year":"2020","journal-title":"Int. Journal Biological Sciences"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1038\/s41419-021-04300-8","article-title":"DCAF1-targeting microRNA-3175 activates Nrf2 signaling and inhibits dexamethasone-induced oxidative injury in human osteoblasts","volume":"12","author":"Chen","year":"2021","journal-title":"Cell Death Dis."},{"key":"B6","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1038\/s41420-023-01560-5","article-title":"Research progress on post-translational modification of proteins and cardiovascular diseases","volume":"9","author":"Cheng","year":"2023","journal-title":"Cell Death Discovery"},{"key":"B7","doi-asserted-by":"publisher","first-page":"S41","DOI":"10.1016\/j.arth.2025.05.091","article-title":"How are diabetes, statins, and immunosuppressive medications linked to non-traumatic osteonecrosis of the femoral head in kidney transplant recipients?","volume":"40","author":"Cheng","year":"2025","journal-title":"J. Arthroplasty"},{"key":"B8","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.molmed.2019.09.007","article-title":"Nrf2: redox and metabolic regulator of stem cell state and function","volume":"26","author":"Dai","year":"2020","journal-title":"Trends Mol. Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"363","DOI":"10.3390\/ijms22010363","article-title":"Inflammation-induced protein unfolding in airway smooth muscle triggers a homeostatic response in mitochondria","volume":"22","author":"Dasgupta","year":"2020","journal-title":"Int. Journal Molecular Sciences"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1787","DOI":"10.3389\/fphys.2018.01787","article-title":"Sesamin protects the femoral head from osteonecrosis by inhibiting ROS-induced osteoblast apoptosis in rat model","volume":"9","author":"Deng","year":"2018","journal-title":"Front. Physiol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1186\/s13287-022-03027-3","article-title":"C\/EBP\u03b1 regulates the fate of bone marrow mesenchymal stem cells and steroid-induced avascular necrosis of the femoral head by targeting the PPAR\u03b3 signalling pathway","volume":"13","author":"Duan","year":"2022","journal-title":"Stem Cell Res. Ther."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1495221","DOI":"10.3389\/fimmu.2024.1495221","article-title":"The role of histone post-translational modifications in cancer and cancer immunity: functions, mechanisms and therapeutic implications","volume":"15","author":"Duan","year":"2024","journal-title":"Front. Immunology"},{"key":"B13","doi-asserted-by":"publisher","first-page":"9761","DOI":"10.26355\/eurrev_201911_19539","article-title":"MiR-15b ameliorates SONFH by targeting Smad7 and inhibiting osteogenic differentiation of BMSCs","volume":"23","author":"Fang","year":"2019","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"B14","doi-asserted-by":"publisher","first-page":"116870","DOI":"10.1016\/j.bcp.2025.116870","article-title":"Irisin alleviates steroid-induced vascular dysfunction by regulating the \u03b1V\u03b25-c-Abl-Caveolin-1 signaling pathway","volume":"236","author":"Fang","year":"2025","journal-title":"Biochem. Pharmacol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1007\/s10495-017-1383-1","article-title":"Fludarabine inhibits STAT1-mediated up-regulation of caspase-3 expression in dexamethasone-induced osteoblasts apoptosis and slows the progression of steroid-induced avascular necrosis of the femoral head in rats","volume":"22","author":"Feng","year":"2017","journal-title":"Apoptosis"},{"key":"B16","doi-asserted-by":"publisher","first-page":"2614","DOI":"10.3390\/ijms18122614","article-title":"The FKBP51 glucocorticoid receptor co-chaperone: Regulation, function, and implications in health and disease","volume":"18","author":"Fries","year":"2017","journal-title":"Int. J. Mol. Sci."},{"key":"B17","doi-asserted-by":"publisher","first-page":"2628","DOI":"10.3390\/ijms19092628","article-title":"Actin-myosin interaction: structure, function and drug discovery","volume":"19","author":"Guhathakurta","year":"2018","journal-title":"Int. Journal Molecular Sciences"},{"key":"B18","doi-asserted-by":"publisher","first-page":"6611","DOI":"10.1021\/jacs.8b02668","article-title":"Protein semisynthesis provides access to tau disease-associated post-translational modifications (PTMs) and paves the way to deciphering the tau PTM code in health and diseased states","volume":"140","author":"Haj-Yahya","year":"2018","journal-title":"J. Am. Chem. Soc."},{"key":"B19","doi-asserted-by":"publisher","first-page":"15803","DOI":"10.3390\/ijms232415803","article-title":"Implications of post-translational modifications in autoimmunity with emphasis on citrullination, homocitrullination and acetylation for the pathogenesis, diagnosis and prognosis of rheumatoid arthritis","volume":"23","author":"Haro","year":"2022","journal-title":"Int. Journal Molecular Sciences"},{"key":"B20","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1146\/annurev.biochem.67.1.425","article-title":"The ubiquitin system","volume":"67","author":"Hershko","year":"1998","journal-title":"Annu. Rev. Biochem."},{"key":"B21","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1007\/s00011-019-01229-9","article-title":"Roles of eNOS in atherosclerosis treatment","volume":"68","author":"Hong","year":"","journal-title":"Inflamm. Res. official J. Eur. Histamine Res. Soc. [et al]"},{"key":"B22","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1016\/j.bbrc.2019.07.095","article-title":"Dysregulation of cPWWP2A-miR-579 axis mediates dexamethasone-induced cytotoxicity in human osteoblasts","volume":"517","author":"Hong","year":"","journal-title":"Biochem. Biophys Res Commun"},{"key":"B23","doi-asserted-by":"publisher","first-page":"25","DOI":"10.3390\/ijms26010025","article-title":"Regulation of histone acetylation modification on biosynthesis of secondary metabolites in fungi","volume":"26","author":"Hou","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B24","doi-asserted-by":"publisher","first-page":"116533","DOI":"10.1016\/j.bcp.2024.116533","article-title":"The blockade of neddylation alleviates ventilator-induced lung injury by reducing stretch-induced damage to pulmonary epithelial cells","volume":"229","author":"Huang","year":"","journal-title":"Biochemical Pharmacology"},{"key":"B25","doi-asserted-by":"publisher","first-page":"e33867","DOI":"10.1016\/j.heliyon.2024.e33867","article-title":"CHRDL2 activates the PI3K\/AKT pathway to ameliorate glucocorticoid-induced damages to bone microvascular endothelial cells (BMECs)","volume":"10","author":"Huang","year":"","journal-title":"Heliyon"},{"key":"B26","doi-asserted-by":"publisher","first-page":"4449","DOI":"10.1021\/acs.biochem.0c00450","article-title":"Post-translational modifications of platelet-derived amyloid precursor protein by coagulation factor XIII-A","volume":"59","author":"Hur","year":"2020","journal-title":"Biochemistry"},{"key":"B27","doi-asserted-by":"publisher","first-page":"20150725","DOI":"10.1259\/bjr.20150725","article-title":"Clinical and imaging features of a subchondral insufficiency fracture of the femoral head after internal fixation of a femoral neck fracture: a comparison with those of post-traumatic osteonecrosis of the femoral head","volume":"89","author":"Ikemura","year":"2016","journal-title":"Br J Radiol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1016\/j.bbrc.2015.02.007","article-title":"K6PC-5, a novel sphingosine kinase 1 (SphK1) activator, alleviates dexamethasone-induced damages to osteoblasts through activating SphK1-Akt signaling","volume":"458","author":"Ji","year":"2015","journal-title":"Biochem. Biophys Res Commun"},{"key":"B29","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1186\/s13018-025-05697-0","article-title":"Icariin promotes osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) by activating PI3K-AKT-UTX\/EZH2 signaling in steroid-induced femoral head osteonecrosis","volume":"20","author":"Ji","year":"2025","journal-title":"J Orthop Surg Res"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1839","DOI":"10.1097\/CM9.0000000000002113","article-title":"Baicalin attenuates dexamethasone-induced apoptosis of bone marrow mesenchymal stem cells by activating the hedgehog signaling pathway","volume":"136","author":"Jia","year":"2023","journal-title":"Chin Med J (Engl)"},{"key":"B31","doi-asserted-by":"publisher","first-page":"e11550","DOI":"10.1590\/1414-431X2021e11550","article-title":"Radiotherapy-induced bone deterioration is exacerbated in diabetic rats treated with streptozotocin","volume":"54","author":"Jiang","year":"2021","journal-title":"Braz J Med Biol Res"},{"key":"B32","doi-asserted-by":"publisher","first-page":"112969","DOI":"10.1016\/j.celrep.2023.112969","article-title":"LncRNA DGCR5-encoded polypeptide RIP aggravates SONFH by repressing nuclear localization of \u03b2-catenin in BMSCs","volume":"42","author":"Jiang","year":"2023","journal-title":"Cell Rep"},{"key":"B33","doi-asserted-by":"publisher","first-page":"sxae069","DOI":"10.1093\/stmcls\/sxae069","article-title":"USP13 overexpression in BMSCs enhances anti-apoptotic ability and guards against methylprednisolone-induced osteonecrosis in rats","volume":"43","author":"Jiang","year":"2025","journal-title":"Stem Cells"},{"key":"B34","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1586\/14779072.5.3.441","article-title":"Hypertension: endothelial dysfunction, the prothrombotic state and antithrombotic therapy","volume":"5","author":"Kakar","year":"2007","journal-title":"Expert Rev Cardiovasc Ther"},{"key":"B35","first-page":"557","article-title":"Macroscopic and microscopic findings in avascular necrosis of the femoral head","volume":"53","author":"Kamal","year":"2012","journal-title":"Rom J Morphol Embryol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"e5138","DOI":"10.1002\/pro.5138","article-title":"Dissecting the functional behavior of the differentially phosphorylated prolyl isomerase, Pin1","volume":"33","author":"Kay","year":"2024","journal-title":"Protein Sci"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20081803","article-title":"The ERK MAPK pathway is essential for skeletal development and homeostasis","volume":"20","author":"Kim","year":"2019","journal-title":"International Journal of Molecular Sciences"},{"key":"B38","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1016\/j.tibs.2017.09.002","article-title":"The ubiquitin code in the ubiquitin-proteasome system and autophagy","volume":"42","author":"Kwon","year":"2017","journal-title":"Trends Biochem. Sci"},{"key":"B39","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.toxlet.2023.04.002","article-title":"The Lnc-HOTAIR\/miR122\/PPAR\u03b3 signaling mediated the occurrence and continuous development of alcohol-induced osteonecrosis of the femoral head","volume":"380","author":"Le","year":"2023","journal-title":"Toxicology Letters"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.12405","article-title":"Emerging roles of MicroRNAs in osteonecrosis of the femoral head","volume":"51","author":"Li","year":"","journal-title":"Cell Proliferation"},{"key":"B41","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1038\/s41598-017-00143-6","article-title":"Proteomic analysis of proteome and histone post-translational modifications in heat shock protein 90 inhibition-mediated bladder cancer therapeutics","volume":"7","author":"Li","year":"","journal-title":"Sci Rep"},{"key":"B42","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1007\/s11626-020-00487-w","article-title":"Crocin promotes osteogenesis differentiation of bone marrow mesenchymal stem cells","volume":"56","author":"Li","year":"2020","journal-title":"Vitro Cell Dev Biol Anim"},{"key":"B43","doi-asserted-by":"publisher","first-page":"2416070","DOI":"10.1080\/07853890.2024.2416070","article-title":"Pathological mechanisms and related markers of steroid-induced osteonecrosis of the femoral head","volume":"56","author":"Li","year":"","journal-title":"Ann Med"},{"key":"B44","doi-asserted-by":"publisher","first-page":"7374","DOI":"10.62347\/CHGJ7909","article-title":"miR-129-5p targets HOXC10 to control BMSC adipogenesis and osteogenesis in a model of steroid-induced osteonecrosis of the femoral head","volume":"16","author":"Li","year":"","journal-title":"Am J Transl Res"},{"key":"B45","doi-asserted-by":"publisher","first-page":"2491846","DOI":"10.1080\/13510002.2025.2491846","article-title":"Update on the correlation between mitochondrial function and osteonecrosis of the Femoral head osteocytes","volume":"30","author":"Li","year":"2025","journal-title":"Redox Rep"},{"key":"B46","doi-asserted-by":"publisher","first-page":"49","DOI":"10.3892\/mmr.2025.13759","article-title":"NEDD4 regulates VEGF signaling and mTOR to promote angiogenesis and the cell cycle in steroid-induced osteonecrosis of the femoral head","volume":"33","author":"Li","year":"2026","journal-title":"Mol Med Rep"},{"key":"B47","doi-asserted-by":"publisher","first-page":"307","DOI":"10.3389\/fphys.2018.00307","article-title":"Pravastatin protects against avascular necrosis of femoral head via autophagy","volume":"9","author":"Liao","year":"2018","journal-title":"Front Physiol"},{"key":"B48","doi-asserted-by":"publisher","first-page":"4270","DOI":"10.1021\/acs.jafc.4c09284","article-title":"Astaxanthin prevents glucocorticoid-induced femoral head osteonecrosis by targeting ferroptosis through the JAK2\/STAT3 signaling pathway","volume":"73","author":"Lin","year":"2025","journal-title":"J Agric Food Chem"},{"key":"B49","doi-asserted-by":"publisher","first-page":"5062","DOI":"10.1038\/s41598-017-05488-6","article-title":"eIF2\u03b1 signaling regulates ischemic osteonecrosis through endoplasmic reticulum stress","volume":"7","author":"Liu","year":"2017","journal-title":"Sci Rep"},{"key":"B50","doi-asserted-by":"publisher","first-page":"1202888","DOI":"10.3389\/fcell.2023.1202888","article-title":"Dragon blood resin ameliorates steroid-induced osteonecrosis of femoral head through osteoclastic pathways","volume":"11","author":"Liu","year":"2023","journal-title":"Front Cell Dev Biol"},{"key":"B51","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1186\/s12964-023-01380-1","article-title":"Crosstalk between protein post-translational modifications and phase separation","volume":"22","author":"Liu","year":"2024","journal-title":"Cell Commun Signal"},{"key":"B52","doi-asserted-by":"publisher","first-page":"37347","DOI":"10.18632\/oncotarget.8135","article-title":"Post-translational modification-regulated leukocyte adhesion and migration","volume":"7","author":"Loh","year":"2016","journal-title":"Oncotarget"},{"key":"B53","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1530\/EOR-22-0092","article-title":"Sclerotic zone in femoral head necrosis: from pathophysiology to therapeutic implications","volume":"8","author":"Lou","year":"2023","journal-title":"EFORT Open Rev"},{"key":"B54","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1111\/os.13970","article-title":"Analysis of the potential angiogenic mechanisms of BuShenHuoXue decoction against osteonecrosis of the Femoral head based on network pharmacology and experimental validation","volume":"16","author":"Luo","year":"2024","journal-title":"Orthop Surg"},{"key":"B55","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/rb\/rbz048","article-title":"Application of biomaterials for the repair and treatment of osteonecrosis of the femoral head","volume":"7","author":"Ma","year":"2020","journal-title":"Regenerative Biomaterials"},{"key":"B56","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/s40709-018-0079-1","article-title":"Changes in the microstructure of compact and trabecular bone tissues of mice subchronically exposed to alcohol","volume":"25","author":"Martiniakova","year":"2018","journal-title":"J Biol Res (Thessalon)"},{"key":"B57","doi-asserted-by":"crossref","first-page":"47","DOI":"10.15406\/jlprr.2021.08.00250","article-title":"Regulation of ACE-2 enzyme by hyperoxia in lung epithelial cells by post-translational modification","volume":"8","author":"Mohamed","year":"2021","journal-title":"Journal of Lung, Pulmonary and Respiratory Research"},{"key":"B58","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1016\/j.bbrc.2019.02.118","article-title":"Glucocorticoid induces osteonecrosis of the femoral head in rats through GSK3\u03b2-mediated osteoblast apoptosis","volume":"511","author":"Nie","year":"2019","journal-title":"Biochem. Biophys Res Commun"},{"key":"B59","doi-asserted-by":"publisher","first-page":"601926","DOI":"10.3389\/fimmu.2020.601926","article-title":"Cellular and mathematical analyses of LUBAC involvement in T cell receptor-mediated NF-\u03baB activation pathway","volume":"11","author":"Oikawa","year":"2020","journal-title":"Frontiers in Immunology"},{"key":"B60","doi-asserted-by":"publisher","first-page":"350","DOI":"10.3390\/antiox12020350","article-title":"Pleiotropic roles of a KEAP1-Associated deubiquitinase, OTUD1","volume":"12","author":"Oikawa","year":"2023","journal-title":"Antioxidants (Basel)"},{"key":"B61","doi-asserted-by":"publisher","first-page":"2109","DOI":"10.1007\/s10787-024-01486-z","article-title":"Epi-revolution in rheumatology: the potential of histone deacetylase inhibitors for targeted rheumatoid arthritis intervention","volume":"32","author":"Pai","year":"2024","journal-title":"Inflammopharmacology"},{"key":"B62","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1186\/s13018-025-06138-8","article-title":"The bibliometric and visualization analysis of alcohol-induced osteonecrosis of the femoral head: research trends and future directions (1998-2024)","volume":"20","author":"Pang","year":"2025","journal-title":"J Orthop Surg Res"},{"key":"B63","doi-asserted-by":"publisher","first-page":"e0125731","DOI":"10.1371\/journal.pone.0125731","article-title":"Parathyroid hormone induces bone cell motility and loss of mature osteocyte phenotype through L-Calcium channel dependent and independent mechanisms","volume":"10","author":"Prideaux","year":"2015","journal-title":"PLoS One"},{"key":"B64","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/bs.acr.2020.05.002","article-title":"Biology, pathology, and therapeutic targeting of RAS","volume":"148","author":"Rhett","year":"2020","journal-title":"Adv Cancer Res"},{"key":"B65","doi-asserted-by":"publisher","first-page":"e13485","DOI":"10.1111\/cpr.13485","article-title":"Effects of astragaloside IV on glucocorticoid-induced avascular necrosis of the femoral head via regulating Akt-related pathways","volume":"56","author":"Shan","year":"2023","journal-title":"Cell Prolif"},{"key":"B66","doi-asserted-by":"publisher","first-page":"e70086","DOI":"10.1002\/kjm2.70086","article-title":"Regulatory effect and mechanism of tanshinone I on cell apoptosis in steroid-induced osteonecrosis of the femoral head","volume":"41","author":"Su","year":"2025","journal-title":"Kaohsiung J Med Sci"},{"key":"B67","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1038\/s41419-021-04313-3","article-title":"Activation of cannabinoid receptor 2 alleviates glucocorticoid-induced osteonecrosis of femoral head with osteogenesis and maintenance of blood supply","volume":"12","author":"Sun","year":"2021","journal-title":"Cell Death Dis"},{"key":"B68","doi-asserted-by":"publisher","first-page":"4988","DOI":"10.1007\/s12011-023-04048-6","article-title":"Ortho-silicic acid prevents glucocorticoid-induced femoral head necrosis by promoting akt phosphorylation to inhibit endoplasmic reticulum stress-mediated apoptosis and enhance angiogenesis and osteogenesis","volume":"202","author":"Sun","year":"2024","journal-title":"Biol Trace Elem Res"},{"key":"B69","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1038\/cr.2016.39","article-title":"Ubiquitin modifications","volume":"26","author":"Swatek","year":"2016","journal-title":"Cell Res"},{"key":"B70","doi-asserted-by":"publisher","first-page":"102489","DOI":"10.1016\/j.arr.2024.102489","article-title":"Unraveling the protein post-translational modification landscape: neuroinflammation and neuronal death after stroke","volume":"101","author":"Tao","year":"","journal-title":"Ageing Research Reviews"},{"key":"B71","doi-asserted-by":"publisher","first-page":"1784","DOI":"10.14336\/AD.2023.0924","article-title":"The emerging role of the mitochondrial respiratory chain in skeletal aging","volume":"15","author":"Tao","year":"","journal-title":"Aging Dis"},{"key":"B72","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.1038\/labinvest.2012.89","article-title":"The suppression of TRIM21 and the accumulation of IFN-\u03b1 play crucial roles in the pathogenesis of osteonecrosis of the femoral head","volume":"92","author":"Tateda","year":"2012","journal-title":"Lab Invest."},{"key":"B73","doi-asserted-by":"publisher","first-page":"102160","DOI":"10.1016\/j.rpth.2023.102160","article-title":"New insight into the traditional model of the coagulation Cascade and its regulation: illustrated review of a three-dimensional view","volume":"7","author":"Troisi","year":"2023","journal-title":"Research and Practice in Thrombosis and Haemostasis"},{"key":"B74","doi-asserted-by":"publisher","first-page":"806","DOI":"10.3390\/jcm11030806","article-title":"The role of sclerostin in bone diseases","volume":"11","author":"Vasiliadis","year":"2022","journal-title":"J Clin Med"},{"key":"B75","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1038\/s41392-023-01439-y","article-title":"Targeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapies","volume":"8","author":"Wu","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"B76","doi-asserted-by":"publisher","first-page":"102337","DOI":"10.1016\/j.jvsv.2025.102337","article-title":"Complex decongestive therapy combined with needle electrode stimulation facilitates postoperative rehabilitation of lymphedema","volume":"14","author":"Wu","year":"2025","journal-title":"Journal of Vascular Surgery Venous and Lymphatic Disorders"},{"key":"B77","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1186\/s12891-023-06992-9","article-title":"Femoral neck fracture after femoral head necrosis: a case report and review of the literature","volume":"24","author":"Xia","year":"2023","journal-title":"BMC Musculoskelet Disord"},{"key":"B78","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.addr.2016.05.003","article-title":"Loops and layers of post-translational modifications of drug transporters","volume":"116","author":"Xu","year":"2017","journal-title":"Adv Drug Deliv Rev"},{"key":"B79","doi-asserted-by":"crossref","first-page":"171","DOI":"10.3892\/ijmm.2020.4788","article-title":"LINC00473 rescues human bone marrow mesenchymal stem cells from apoptosis induced by dexamethasone through the PEBP1-mediated Akt\/Bad\/Bcl-2 signaling pathway","volume":"47","author":"Xu","year":"2021","journal-title":"Int J Mol Med"},{"key":"B80","doi-asserted-by":"publisher","first-page":"109965","DOI":"10.1016\/j.exer.2024.109965","article-title":"IP3R2 regulates apoptosis by Ca2+ transfer through mitochondria-ER contacts in hypoxic photoreceptor injury","volume":"245","author":"Xu","year":"2024","journal-title":"Exp Eye Res"},{"key":"B81","doi-asserted-by":"publisher","first-page":"1643316","DOI":"10.3389\/fphar.2025.1643316","article-title":"In situ sustained release of icariin from injectable thermosensitive PLGA-PEG-PLGA hydrogels combined with core decompression for steroid-induced osteonecrosis of femoral head","volume":"16","author":"Xu","year":"2025","journal-title":"Front Pharmacol"},{"key":"B82","doi-asserted-by":"publisher","first-page":"3751","DOI":"10.3892\/mmr.2017.8349","article-title":"Salidroside inhibits steroid-induced avascular necrosis of the femoral head via the PI3K\/Akt signaling pathway: In vitro and in vivo studies","volume":"17","author":"Xue","year":"2018","journal-title":"Mol Med Rep"},{"key":"B83","doi-asserted-by":"publisher","first-page":"3456","DOI":"10.1111\/os.70191","article-title":"Selenium attenuates dexamethasone-induced osteoblast dysfunction and prevents femoral head osteonecrosis via PI3K\/AKT\/GSK3\u03b2 pathway activation","volume":"17","author":"Xuecheng","year":"2025","journal-title":"Orthop Surg"},{"key":"B84","doi-asserted-by":"publisher","first-page":"237","DOI":"10.5301\/hipint.5000224","article-title":"Does osteonecrosis of the femoral head increase surgical and medical complication rates after total hip arthroplasty? A comprehensive analysis in the United States","volume":"25","author":"Yang","year":"2015","journal-title":"Hip Int"},{"key":"B85","doi-asserted-by":"publisher","first-page":"1416967","DOI":"10.3389\/fphys.2024.1416967","article-title":"The role of O-GlcNAcylation in bone metabolic diseases","volume":"15","author":"Yang","year":"2024","journal-title":"Front Physiol"},{"key":"B86","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/s41232-023-00268-4","article-title":"JAK inhibition ameliorates bone destruction by simultaneously targeting mature osteoclasts and their precursors","volume":"43","author":"Yari","year":"2023","journal-title":"Inflammation and Regeneration"},{"key":"B87","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1186\/s13018-025-05912-y","article-title":"Decreased serum and local GPX4 and SLC7A11 expression correlates with disease severity in non-traumatic osteonecrosis of the femoral head","volume":"20","author":"Ye","year":"2025","journal-title":"J Orthop Surg Res"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20133147","article-title":"Bone remodeling: Histone modifications as fate determinants of bone cell differentiation","volume":"20","author":"Yi","year":"2019","journal-title":"International Journal of Molecular Sciences"},{"key":"B89","doi-asserted-by":"publisher","first-page":"1626617","DOI":"10.3389\/fimmu.2025.1626617","article-title":"Immunological mechanisms in steroid-induced osteonecrosis of the femoral head","volume":"16","author":"Yin","year":"2025","journal-title":"Front Immunol"},{"key":"B90","doi-asserted-by":"publisher","first-page":"e3207","DOI":"10.1002\/jgm.3207","article-title":"\u03b2-ecdysone promotes osteogenic differentiation of bone marrow mesenchymal stem cells","volume":"22","author":"You","year":"2020","journal-title":"J Gene Med"},{"key":"B91","doi-asserted-by":"publisher","first-page":"1264","DOI":"10.3892\/ijmm.2015.2340","article-title":"Lithium chloride attenuates the abnormal osteogenic\/adipogenic differentiation of bone marrow-derived mesenchymal stem cells obtained from rats with steroid-related osteonecrosis by activating the \u03b2-catenin pathway","volume":"36","author":"Yu","year":"2015","journal-title":"Int J Mol Med"},{"key":"B92","doi-asserted-by":"publisher","first-page":"3043","DOI":"10.3390\/cells11193043","article-title":"Post-translational modifications of cGAS-STING: a critical switch for immune regulation","volume":"11","author":"Yu","year":"2022","journal-title":"Cells"},{"key":"B93","doi-asserted-by":"publisher","first-page":"0759","DOI":"10.34133\/research.0759","article-title":"Neonatal-inspired reprogramming of microglial pan-programmed cell death enhances regeneration in adult spinal cord injury","volume":"8","author":"Yu","year":"2025","journal-title":"Research (Wash D C)"},{"key":"B94","doi-asserted-by":"publisher","first-page":"675617","DOI":"10.3389\/fcell.2021.675617","article-title":"Fatty acids metabolism: the bridge between ferroptosis and ionizing radiation","volume":"9","author":"Yuan","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"B95","doi-asserted-by":"publisher","first-page":"9060143","DOI":"10.1155\/2016\/9060143","article-title":"Platelet activation: the mechanisms and potential biomarkers","volume":"2016","author":"Yun","year":"2016","journal-title":"BioMed Research International"},{"key":"B96","doi-asserted-by":"publisher","first-page":"4109","DOI":"10.1016\/j.biomaterials.2011.02.036","article-title":"The role of single cell derived vascular resident endothelial progenitor cells in the enhancement of vascularization in scaffold-based skin regeneration","volume":"32","author":"Zhang","year":"2011","journal-title":"Biomaterials"},{"key":"B97","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1038\/s41419-020-2238-1","article-title":"P53 and parkin co-regulate mitophagy in bone marrow mesenchymal stem cells to promote the repair of early steroid-induced osteonecrosis of the femoral head","volume":"11","author":"Zhang","year":"2020","journal-title":"Cell Death Dis"},{"key":"B98","doi-asserted-by":"publisher","first-page":"109821","DOI":"10.1016\/j.celrep.2021.109821","article-title":"Homocysteine inhibits pro-insulin receptor cleavage and causes insulin resistance via protein cysteine-homocysteinylation","volume":"37","author":"Zhang","year":"2021","journal-title":"Cell Reports"},{"key":"B99","doi-asserted-by":"publisher","first-page":"10","DOI":"10.12122\/j.issn.1673-4254.2025.01.02","article-title":"HDAC1 overexpression inhibits steroid-induced apoptosis of mouse osteocyte-like MLO-Y4 cells by inducing SP1 deacetylation","volume":"45","author":"Zhang","year":"2025","journal-title":"Nan Fang Yi Ke Da Xue Xue Bao"},{"key":"B100","doi-asserted-by":"publisher","first-page":"2059","DOI":"10.4103\/0366-6999.161364","article-title":"Early outcomes of primary total hip arthroplasty for osteonecrosis of the femoral head in patients with human immunodeficiency virus in China","volume":"128","author":"Zhao","year":"2015","journal-title":"Chin Med J (Engl)"},{"key":"B101","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.biomaterials.2015.11.038","article-title":"Vascularized bone grafting fixed by biodegradable magnesium screw for treating osteonecrosis of the femoral head","volume":"81","author":"Zhao","year":"2016","journal-title":"Biomaterials"},{"key":"B102","doi-asserted-by":"publisher","first-page":"1581085","DOI":"10.3389\/fphar.2025.1581085","article-title":"Metformin improves intestinal ischemia-reperfusion injury by reducing the formation of mitochondrial associated endoplasmic reticulum membranes (MAMs) and inhibiting ferroptosis in intestinal cells","volume":"16","author":"Zhao","year":"2025","journal-title":"Front Pharmacol"},{"key":"B103","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1146\/annurev-biochem-060815-014922","article-title":"Ubiquitin ligases: structure, function, and regulation","volume":"86","author":"Zheng","year":"2017","journal-title":"Annu. Rev Biochem."},{"key":"B104","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1186\/s13018-024-04713-z","article-title":"Non-traumatic osteonecrosis of the femoral head induced by steroid and alcohol exposure is associated with intestinal flora alterations and metabolomic profiles","volume":"19","author":"Zheng","year":"2024","journal-title":"J Orthop Surg Res"},{"key":"B105","doi-asserted-by":"publisher","first-page":"e261","DOI":"10.1002\/mco2.261","article-title":"Protein posttranslational modifications in health and diseases: functions, regulatory mechanisms, and therapeutic implications","volume":"4","author":"Zhong","year":"2023","journal-title":"MedComm"}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2026.1885721\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T08:12:46Z","timestamp":1786954366000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2026.1885721\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,17]]},"references-count":105,"alternative-id":["10.3389\/fcell.2026.1885721"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2026.1885721","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,17]]},"article-number":"1885721"}}