{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T19:51:21Z","timestamp":1791748281210,"version":"4.3.4"},"reference-count":56,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T00:00:00Z","timestamp":1691107200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004515","name":"Universiti Kebangsaan Malaysia","doi-asserted-by":"publisher","award":["GUP-2021-034"],"award-info":[{"award-number":["GUP-2021-034"]}],"id":[{"id":"10.13039\/501100004515","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A positive association between insulin resistance and osteoporosis has been widely established. However, crosstalk between the signalling molecules in insulin and Wingless (Wnt)\/beta-(\u03b2-)catenin transduction cascades orchestrating bone homeostasis remains not well understood. The current review aims to collate the existing evidence, reporting (a) the expression of insulin signalling molecules involved in bone-related disorders and (b) the expression of Wnt\/\u03b2-catenin signalling molecules involved in governing insulin homeostasis. The downstream effector molecule, glycogen synthase kinase-3 beta (GSK3\u03b2), has been identified to be a point of convergence linking the two signal transduction networks. This review highlights that GSK3\u03b2 may be a drug target in the development of novel anabolic agents and the potential use of GSK3\u03b2 inhibitors to treat bone-related disorders.<\/jats:p>","DOI":"10.3390\/ijms241512441","type":"journal-article","created":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T09:27:48Z","timestamp":1691141268000},"page":"12441","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["A Review on the Crosstalk between Insulin and Wnt\/\u03b2-Catenin Signalling for Bone Health"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1184-4551","authenticated-orcid":false,"given":"Sok Kuan","family":"Wong","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6254-5132","authenticated-orcid":false,"given":"Nur Vaizura","family":"Mohamad","sequence":"additional","affiliation":[{"name":"Centre for Drug and Herbal Development, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9742-160X","authenticated-orcid":false,"given":"Putri Ayu","family":"Jayusman","sequence":"additional","affiliation":[{"name":"Department of Craniofacial Diagnostics and Biosciences, Faculty of Dentistry, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2486-9486","authenticated-orcid":false,"given":"Nurul \u2018Izzah","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,4]]},"reference":[{"key":"ref_1","first-page":"421746","article-title":"Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells","volume":"2015","author":"Sasso","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.cell.2010.06.003","article-title":"Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism","volume":"142","author":"Ferron","year":"2010","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S8756-3282(98)00095-7","article-title":"Insulin receptor expression in primary and cultured osteoclast-like cells","volume":"23","author":"Thomas","year":"1998","journal-title":"Bone"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Campillo-S\u00e1nchez, F., Usategui-Mart\u00edn, R., Ruiz-de Temi\u00f1o, \u00c1., Gil, J., Ruiz-Mambrilla, M., Fern\u00e1ndez-G\u00f3mez, J.M., Due\u00f1as-Laita, A., and P\u00e9rez-Castrill\u00f3n, J.L. (2020). Relationship between Insulin Resistance (HOMA-IR), Trabecular Bone Score (TBS), and Three-Dimensional Dual-Energy X-ray Absorptiometry (3D-DXA) in Non-Diabetic Postmenopausal Women. J. Clin. Med., 9.","DOI":"10.3390\/jcm9061732"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"971960","DOI":"10.3389\/fendo.2022.971960","article-title":"Associations of insulin resistance and insulin secretion with bone mineral density and osteoporosis in a general population","volume":"13","author":"Fu","year":"2022","journal-title":"Front. Endocrinol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.2147\/DMSO.S302627","article-title":"Association of Insulin Glargine Treatment with Bone Mineral Density in Patients with Type 2 Diabetes Mellitus","volume":"14","author":"Liu","year":"2021","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.bone.2018.07.003","article-title":"Exploring the potential of tocotrienol from Bixa orellana as a single agent targeting metabolic syndrome and bone loss","volume":"116","author":"Wong","year":"2018","journal-title":"Bone"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Wong, S.K., Chin, K.Y., Suhaimi, F.H., Ahmad, F., and Ima-Nirwana, S. (2018). The Effects of Vitamin E from Elaeis guineensis (Oil Palm) in a Rat Model of Bone Loss Due to Metabolic Syndrome. Int. J. Environ. Res. Public Health, 15.","DOI":"10.3390\/ijerph15091828"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2701","DOI":"10.17576\/jsm-2019-4812-11","article-title":"Leptin, adiponectin and insulin as regulators for energy metabolism in a rat model of metabolic syndrome","volume":"48","author":"Wong","year":"2019","journal-title":"Sains Malays."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.jff.2018.03.022","article-title":"The effects of palm tocotrienol on metabolic syndrome and bone loss in male rats induced by high-carbohydrate high-fat diet","volume":"44","author":"Wong","year":"2018","journal-title":"J. Funct. Foods"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.biopha.2017.12.042","article-title":"Osteoporosis is associated with metabolic syndrome induced by high-carbohydrate high-fat diet in a rat model","volume":"98","author":"Wong","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1007\/s12020-017-1396-0","article-title":"Insulin and osteocalcin: Further evidence for a mutual cross-talk","volume":"59","author":"Bilotta","year":"2018","journal-title":"Endocrine"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e1552","DOI":"10.1210\/clinem\/dgaa963","article-title":"Insulin-like Growth Factor-1, Bone Mineral Density, and Fracture: A Mendelian Randomization Study","volume":"106","author":"Yuan","year":"2021","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1007\/s11357-016-9902-5","article-title":"Differential effects of IGF-1 deficiency during the life span on structural and biomechanical properties in the tibia of aged mice","volume":"38","author":"Ashpole","year":"2016","journal-title":"Age"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"794","DOI":"10.3389\/fendo.2018.00794","article-title":"Osteocalcin-A Versatile Bone-Derived Hormone","volume":"9","author":"Moser","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41392-021-00762-6","article-title":"Wnt\/\u03b2-catenin signalling: Function, biological mechanisms, and therapeutic opportunities","volume":"7","author":"Liu","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1111\/jnc.15277","article-title":"Activation of Wnt\/\u03b2-catenin signaling restores insulin sensitivity in insulin resistant neurons through transcriptional regulation of IRS-1","volume":"157","author":"Tian","year":"2021","journal-title":"J. Neurochem."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Rahman, M.S., Hossain, K.S., Das, S., Kundu, S., Adegoke, E.O., Rahman, M.A., Hannan, M.A., Uddin, M.J., and Pang, M.G. (2021). Role of Insulin in Health and Disease: An Update. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126403"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3389\/fncel.2017.00014","article-title":"Insulin-Like Growth Factor 1: At the Crossroads of Brain Development and Aging","volume":"11","author":"Wrigley","year":"2017","journal-title":"Front. Cell. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"117","DOI":"10.3389\/fendo.2018.00117","article-title":"IGF-Binding Proteins: Why Do They Exist and Why Are There So Many?","volume":"9","author":"Allard","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"312","DOI":"10.2174\/18715273113126660133","article-title":"A molecular bridge: Connecting type 2 diabetes and Alzheimer\u2019s disease","volume":"13","author":"Ahmed","year":"2014","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1029130","DOI":"10.3389\/fendo.2022.1029130","article-title":"Wnt signaling pathway inhibitors, sclerostin and DKK-1, correlate with pain and bone pathology in patients with Gaucher disease","volume":"13","author":"Ivanova","year":"2022","journal-title":"Front. Endocrinol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.biocel.2016.05.015","article-title":"The role of the wnt\/\u03b2-catenin signaling pathway in formation and maintenance of bone and teeth","volume":"77","author":"Duan","year":"2016","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1515\/jpem-2022-0001","article-title":"Investigation of the relationship between serum sclerostin and dickkopf-1 protein levels with bone turnover in children and adolescents with type-1 diabetes mellitus","volume":"35","author":"Kurban","year":"2022","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"16001","DOI":"10.1038\/boneres.2016.1","article-title":"Assessment of bone turnover and bone quality in type 2 diabetic bone disease: Current concepts and future directions","volume":"4","author":"Rubin","year":"2016","journal-title":"Bone Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1210\/jc.2016-2371","article-title":"High Sclerostin and Dickkopf-1 (DKK-1) Serum Levels in Children and Adolescents with Type 1 Diabetes Mellitus","volume":"102","author":"Faienza","year":"2017","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1530\/EJE-19-0542","article-title":"Effect of insulin resistance on whole blood mRNA and microRNA expression affecting bone turnover","volume":"181","author":"Razny","year":"2019","journal-title":"Eur. J. Endocrinol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1002\/jbmr.1834","article-title":"\u03b2-catenin promotes bone formation and suppresses bone resorption in postnatal growing mice","volume":"28","author":"Chen","year":"2013","journal-title":"J. Bone Miner. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1530\/EC-20-0535","article-title":"Serum sclerostin is negatively associated with insulin sensitivity in obese but not lean women","volume":"10","author":"Aznou","year":"2021","journal-title":"Endocr. Connect."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.2337\/dc14-2989","article-title":"Sclerostin and Insulin Resistance in Prediabetes: Evidence of a Cross Talk between Bone and Glucose Metabolism","volume":"38","author":"Daniele","year":"2015","journal-title":"Diabetes Care"},{"key":"ref_31","first-page":"326","article-title":"Higher plasma sclerostin and lower Wnt signaling gene expression in white adipose tissue of prediabetic South Asian men compared with white Caucasian men","volume":"43","author":"Janssen","year":"2019","journal-title":"Diabetes Metab. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"227","DOI":"10.3389\/fendo.2017.00227","article-title":"Bone Status in a Patient with Insulin-Like Growth Factor-1 Receptor Deletion Syndrome: Bone Quality and Structure Evaluation Using Dual-Energy X-Ray Absorptiometry, Peripheral Quantitative Computed Tomography, and Quantitative Ultrasonography","volume":"8","author":"Pelosi","year":"2017","journal-title":"Front. Endocrinol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.bone.2013.06.029","article-title":"Increased serum sclerostin and decreased serum IGF-1 are associated with vertebral fractures among postmenopausal women with type-2 diabetes","volume":"56","author":"Ardawi","year":"2013","journal-title":"Bone"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"116368","DOI":"10.1016\/j.bone.2022.116368","article-title":"The relationship between circulating hormone levels, bone turnover markers and skeletal development in healthy boys differs according to maturation stage","volume":"158","author":"Banica","year":"2022","journal-title":"Bone"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1631\/jzus.B1800648","article-title":"IGF-1R\/\u03b2-catenin signaling axis is involved in type 2 diabetic osteoporosis","volume":"20","author":"Zhang","year":"2019","journal-title":"J. Zhejiang Univ. Sci. B"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-018-0186-y","article-title":"Differential effects of type 1 diabetes mellitus and subsequent osteoblastic \u03b2-catenin activation on trabecular and cortical bone in a mouse model","volume":"50","author":"Chen","year":"2018","journal-title":"Exp. Mol. Med."},{"key":"ref_37","first-page":"455","article-title":"Insulin-dependent diabetes mellitus decreases osteoblastogenesis associated with the inhibition of Wnt signaling through increased expression of Sost and Dkk1 and inhibition of Akt activation","volume":"28","author":"Hie","year":"2011","journal-title":"Int. J. Mol. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1007\/s12011-015-0555-5","article-title":"Analysis of the Role of Insulin Signaling in Bone Turnover Induced by Fluoride","volume":"171","author":"Liu","year":"2016","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1080\/13697137.2020.1816956","article-title":"IGF-1R\/\u03b2-catenin signaling axis is implicated in streptozotocin exacerbating bone impairment in ovariectomized rats","volume":"24","author":"Zhang","year":"2021","journal-title":"Climacteric"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2280","DOI":"10.1096\/fj.201700998RR","article-title":"IGFBP7 regulates the osteogenic differentiation of bone marrow-derived mesenchymal stem cells via Wnt\/\u03b2-catenin signaling pathway","volume":"32","author":"Zhang","year":"2018","journal-title":"FASEB J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1111\/1756-185X.13050","article-title":"Traditional Chinese medicine Bushen-Jianpi-Huoxue decoction prevents diabetic osteoporosis in rats via Wnt and nuclear factor-kappa B signaling pathways","volume":"20","author":"Zhang","year":"2017","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1159\/000455936","article-title":"Diabetes perturbs bone microarchitecture and bone strength through regulation of Sema3A\/IGF-1\/\u03b2-catenin in rats","volume":"41","author":"Ma","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"110921","DOI":"10.1016\/j.mce.2020.110921","article-title":"GLP-1 promotes osteogenic differentiation of human ADSCs via the Wnt\/GSK-3\u03b2\/\u03b2-catenin pathway","volume":"515","author":"Li","year":"2020","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"233","DOI":"10.11005\/jbm.2014.21.4.233","article-title":"Regulation of NFATc1 in Osteoclast Differentiation","volume":"21","author":"Kim","year":"2014","journal-title":"J. Bone Metab."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1159\/000492549","article-title":"Constitutive Activation of \u03b2-Catenin in Differentiated Osteoclasts Induces Bone Loss in Mice","volume":"48","author":"Sui","year":"2018","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"E271","DOI":"10.1152\/ajpendo.00092.2013","article-title":"Osteocyte-derived insulin-like growth factor I is essential for determining bone mechanosensitivity","volume":"305","author":"Lau","year":"2013","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"14670","DOI":"10.1074\/jbc.M110.193334","article-title":"The heparin-binding domain of IGFBP-2 has insulin-like growth factor binding-independent biologic activity in the growing skeleton","volume":"286","author":"Kawai","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"6899","DOI":"10.1074\/jbc.RA118.006769","article-title":"Lrp4 expression by adipocytes and osteoblasts differentially impacts sclerostin\u2019s endocrine effects on body composition and glucose metabolism","volume":"294","author":"Kim","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3805","DOI":"10.1210\/en.2017-00657","article-title":"Lack of Lrp5 Signaling in Osteoblasts Sensitizes Male Mice to Diet-Induced Disturbances in Glucose Metabolism","volume":"158","author":"Kim","year":"2017","journal-title":"Endocrinology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1073\/pnas.0133792100","article-title":"Low-density lipoprotein receptor-related protein 5 (LRP5) is essential for normal cholesterol metabolism and glucose-induced insulin secretion","volume":"100","author":"Fujino","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1002\/jbmr.4303","article-title":"Gain-of-Function Lrp5 Mutation Improves Bone Mass and Strength and Delays Hyperglycemia in a Mouse Model of Insulin-Deficient Diabetes","volume":"36","author":"Leanza","year":"2021","journal-title":"J. Bone Miner. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"9576","DOI":"10.1074\/jbc.M509205200","article-title":"Up-regulation of the Wnt, estrogen receptor, insulin-like growth factor-I, and bone morphogenetic protein pathways in C57BL\/6J osteoblasts as opposed to C3H\/HeJ osteoblasts in part contributes to the differential anabolic response to fluid shear","volume":"281","author":"Lau","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"8743","DOI":"10.1074\/jbc.M109.027086","article-title":"Mechano-transduction in osteoblastic cells involves strain-regulated estrogen receptor \u03b1-mediated control of insulin-like growth factor (IGF) I receptor sensitivity to ambient IGF, leading to phosphatidylinositol 3-kinase\/AKT-dependent Wnt\/LRP5 receptor-independent activation of \u03b2-catenin signaling","volume":"285","author":"Sunters","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_54","first-page":"347","article-title":"Biological basis of bone strength: Anatomy, physiology and measurement","volume":"20","author":"Hart","year":"2020","journal-title":"J. Musculoskelet. Neuronal. Interact."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"891","DOI":"10.3892\/etm.2021.10323","article-title":"Insulin growth factor-1 promotes the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells through the Wnt\/\u03b2-catenin pathway","volume":"22","author":"Feng","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"14031","DOI":"10.1074\/jbc.M110.102855","article-title":"Activation of canonical wingless-type MMTV integration site family (Wnt) signaling in mature adipocytes increases \u03b2-catenin levels and leads to cell dedifferentiation and insulin resistance","volume":"285","author":"Gustafson","year":"2010","journal-title":"J. Biol. Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/15\/12441\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:26:04Z","timestamp":1760127964000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/15\/12441"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,4]]},"references-count":56,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["ijms241512441"],"URL":"https:\/\/doi.org\/10.3390\/ijms241512441","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,4]]}}}