{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:50:45Z","timestamp":1787237445095,"version":"build-2736575974"},"reference-count":37,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T00:00:00Z","timestamp":1714521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korean Ministry of Health &amp; Welfare","award":["HR22C1363"],"award-info":[{"award-number":["HR22C1363"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Fibrous dysplasia (FD) poses a therapeutic challenge due to the dysregulated extracellular matrix (ECM) accumulation within affected bone tissues. In this study, we investigate the therapeutic potential of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in managing FD by examining its effects on FD-derived cells in vitro. Our findings demonstrate that 1,25(OH)2D3 treatment attenuates the pro-fibrotic phenotype of FD-derived cells by suppressing the expression of key pro-fibrotic markers and inhibiting cell proliferation and migration. Moreover, 1,25(OH)2D3 enhances mineralization by attenuating pre-osteoblastic cellular hyperactivity and promoting maturation towards an osteocytic phenotype. These results offer valuable insights into potential treatments for FD, highlighting the role of 1,25(OH)2D3 in modulating the pathological properties of FD-derived cells.<\/jats:p>","DOI":"10.3390\/ijms25094954","type":"journal-article","created":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T08:59:39Z","timestamp":1714553979000},"page":"4954","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Vitamin D Attenuates Fibrotic Properties of Fibrous Dysplasia-Derived Cells for the Transit towards Osteocytic Phenotype"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7613-5249","authenticated-orcid":false,"given":"Ha-Young","family":"Kim","sequence":"first","affiliation":[{"name":"Interdisciplinary Program in Bioengineering, Seoul National University, Seoul 08826, Republic of Korea"},{"name":"Department of Plastic and Reconstructive Surgery, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung-Hee","family":"Shim","sequence":"additional","affiliation":[{"name":"Department of Research Administration Team, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea"},{"name":"Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baek-Kyu","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea"},{"name":"Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9003-7365","authenticated-orcid":false,"given":"Chan-Yeong","family":"Heo","sequence":"additional","affiliation":[{"name":"Interdisciplinary Program in Bioengineering, Seoul National University, Seoul 08826, Republic of Korea"},{"name":"Department of Plastic and Reconstructive Surgery, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea"},{"name":"Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1002\/jbmr.3602","article-title":"Activation of RANK\/RANKL\/OPG Pathway Is Involved in the Pathophysiology of Fibrous Dysplasia and Associated with Disease Burden","volume":"34","author":"Burke","year":"2019","journal-title":"J. Bone Miner. Res."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Kim, H.-Y., Shim, J.-H., and Heo, C.-Y. (2023). A Rare Skeletal Disorder, Fibrous Dysplasia: A Review of Its Pathogenesis and Therapeutic Prospects. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242115591"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Michel, Z., Raborn, L.N., Spencer, T., Pan, K., Martin, D., Roszko, K.L., Wang, Y., Robey, P.G., Collins, M.T., and Boyce, A.M. (2024). Transcriptomic Signature and Pro-Osteoclastic Secreted Factors of Abnormal Bone Marrow Stromal Cells in Fibrous Dysplasia. bioRxiv.","DOI":"10.1101\/2024.02.23.581225"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Shen, L., He, Y., Chen, S., He, L., and Zhang, Y. (2023). PTHrP Modulates the Proliferation and Osteogenic Differentiation of Craniofacial Fibrous Dysplasia-Derived BMSCs. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24087616"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/07435800902841280","article-title":"GNAS Haploinsufficiency Leads to Subcutaneous Tumor Formation with Collagen and Elastin Deposition and Calcification","volume":"34","author":"Sakamoto","year":"2009","journal-title":"Endocr. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.biomaterials.2016.08.042","article-title":"Pro-Fibrotic Effects of PFKFB4-Mediated Glycolytic Reprogramming in Fibrous Dysplasia","volume":"107","author":"Lee","year":"2016","journal-title":"Biomaterials"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.humpath.2008.07.008","article-title":"Periostin, a Novel Marker of Intramembranous Ossification, Is Expressed in Fibrous Dysplasia and in c-Fos\u2013Overexpressing Bone Lesions","volume":"40","author":"Kashima","year":"2009","journal-title":"Hum. Pathol."},{"key":"ref_8","first-page":"531","article-title":"Frequent Immunoexpression of TGF-\u03921, FGF-2 and BMP-2 in Fibroblast-like Cells in Osteofibrous Dysplasia","volume":"17","author":"Sakamoto","year":"2007","journal-title":"Oncol. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1359\/jbmr.080609","article-title":"Age-Dependent Demise of GNAS -Mutated Skeletal Stem Cells and \u201cNormalization\u201d of Fibrous Dysplasia of Bone","volume":"23","author":"Kuznetsov","year":"2008","journal-title":"J. Bone Miner. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1159\/000430160","article-title":"The Effect of cAMP-PKA Activation on TGF-\u03921-Induced Profibrotic Signaling","volume":"36","author":"Weng","year":"2015","journal-title":"Cell. Physiol. Biochem. Int. J. Exp. Cell. Physiol. Biochem. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1080\/21655979.2020.1860491","article-title":"Activating Transcription Factor 3 (ATF3) Regulates Cell Growth, Apoptosis, Invasion and Collagen Synthesis in Keloid Fibroblast through Transforming Growth Factor Beta (TGF-Beta)\/SMAD Signaling Pathway","volume":"12","author":"Wang","year":"2021","journal-title":"Bioengineered"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/ncb826","article-title":"Connective-Tissue Growth Factor (CTGF) Modulates Cell Signalling by BMP and TGF-Beta","volume":"4","author":"Abreu","year":"2002","journal-title":"Nat. Cell Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.matbio.2015.05.006","article-title":"The Extracellular Matrix and Transforming Growth Factor-\u03921: Tale of a Strained Relationship","volume":"47","author":"Hinz","year":"2015","journal-title":"Matrix Biol. J. Int. Soc. Matrix Biol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Yombo, D.J., Ghandikota, S., Vemulapalli, C.P., Singh, P., Jegga, A.G., Hardie, W.D., and Madala, S.K. (2024). SEMA3B Inhibits TGF\u03b2-Induced Extracellular Matrix Protein Production and Its Reduced Levels Are Associated with a Decline in Lung Function in IPF. Am. J. Physiol. Cell Physiol.","DOI":"10.1152\/ajpcell.00681.2023"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"115784","DOI":"10.1016\/j.bone.2020.115784","article-title":"Bisphosphonates for the Treatment of Fibrous Dysplasia of Bone","volume":"143","author":"Chapurlat","year":"2021","journal-title":"Bone"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"116819","DOI":"10.1016\/j.bone.2023.116819","article-title":"Denosumab Use in Bone Fibrous Dysplasia Refractory to Bisphosphonate: A Retrospective Multicentric Study","volume":"174","author":"Trojani","year":"2023","journal-title":"Bone"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"116343","DOI":"10.1016\/j.bone.2022.116343","article-title":"Inhibition of IL-6 in the Treatment of Fibrous Dysplasia of Bone: The Randomized Double-Blind Placebo-Controlled TOCIDYS Trial","volume":"157","author":"Chapurlat","year":"2022","journal-title":"Bone"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Tucker-Bartley, A., Selen, D.J., Golden, E., Van Gool, R., Ebb, D., Mannstadt, M., and Upadhyay, J. (2023). Pharmacological Interventions Targeting Pain in Fibrous Dysplasia\/McCune\u2013Albright Syndrome. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032550"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"117047","DOI":"10.1016\/j.bone.2024.117047","article-title":"A Pathogenic Role for Brain-Derived Neurotrophic Factor (BDNF) in Fibrous Dysplasia of Bone","volume":"181","author":"Palmisano","year":"2024","journal-title":"Bone"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"9150819","DOI":"10.1155\/2016\/9150819","article-title":"Vitamin D Effects on Osteoblastic Differentiation of Mesenchymal Stem Cells from Dental Tissues","volume":"2016","author":"Posa","year":"2016","journal-title":"Stem Cells Int."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Borojevi\u0107, A., Jaukovi\u0107, A., Kukolj, T., Mojsilovi\u0107, S., Obradovi\u0107, H., Trivanovi\u0107, D., \u017divanovi\u0107, M., Ze\u010devi\u0107, \u017d., Simi\u0107, M., and Gobelji\u0107, B. (2022). Vitamin D3 Stimulates Proliferation Capacity, Expression of Pluripotency Markers, and Osteogenesis of Human Bone Marrow Mesenchymal Stromal\/Stem Cells, Partly through SIRT1 Signaling. Biomolecules, 12.","DOI":"10.3390\/biom12020323"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1080\/17453674.2019.1608117","article-title":"Pain in Fibrous Dysplasia: Relationship with Anatomical and Clinical Features","volume":"90","author":"Majoor","year":"2019","journal-title":"Acta Orthop."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Kim, H.-Y., Charton, C., Shim, J.H., Lim, S.Y., Kim, J., Lee, S., Ohn, J.H., Kim, B.K., and Heo, C.Y. (2024). Patient-Derived Organoids Recapitulate Pathological Intrinsic and Phenotypic Features of Fibrous Dysplasia. Cells, 13.","DOI":"10.3390\/cells13090729"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"967","DOI":"10.3892\/ijmm.2015.2318","article-title":"1\u03b1,25-Dihydroxyvitamin D3 Prevents the Differentiation of Human Lung Fibroblasts via microRNA-27b Targeting the Vitamin D Receptor","volume":"36","author":"Li","year":"2015","journal-title":"Int. J. Mol. Med."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Janjetovic, Z., Qayyum, S., Reddy, S.B., Podgorska, E., Scott, S.G., Szpotan, J., Mobley, A.A., Li, W., Boda, V.K., and Ravichandran, S. (2024). Novel Vitamin D3 Hydroxymetabolites Require Involvement of the Vitamin D Receptor or Retinoic Acid-Related Orphan Receptors for Their Antifibrogenic Activities in Human Fibroblasts. Cells, 13.","DOI":"10.3390\/cells13030239"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Voisin, T., Joannes, A., Morzadec, C., Lagadic-Gossmann, D., Naoures, C.L., De Latour, B.R., Rouze, S., Jouneau, S., and Vernhet, L. (2024). Antifibrotic Effects of Vitamin D3 on Human Lung Fibroblasts Derived from Patients with Idiopathic Pulmonary Fibrosis. J. Nutr. Biochem., 125.","DOI":"10.1016\/j.jnutbio.2023.109558"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Wagenfeld, A., Moeller, C., Sandner, P., Schwede, W., Steinmeyer, A., and Zuegel, U. (2011). Inhibition of Proliferation and Fibrosis by Vitamin D Agonists\u2014Impact for Uterine Leiomyoma. Biol. Reprod., 85.","DOI":"10.1093\/biolreprod\/85.s1.363"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/j.bone.2019.07.026","article-title":"Vitamin D Sterols Increase FGF23 Expression by Stimulating Osteoblast and Osteocyte Maturation in CKD Bone","volume":"127","author":"Pereira","year":"2019","journal-title":"Bone"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s13105-020-00778-6","article-title":"Concurrent Vitamin D Supplementation and Exercise Training Improve Cardiac Fibrosis via TGF-\u03b2\/Smad Signaling in Myocardial Infarction Model of Rats","volume":"77","author":"Mehdipoor","year":"2021","journal-title":"J. Physiol. Biochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"8085","DOI":"10.1038\/s41598-019-44574-9","article-title":"Vitamin D and Wnt3A Have Additive and Partially Overlapping Modulatory Effects on Gene Expression and Phenotype in Human Colon Fibroblasts","volume":"9","author":"Niell","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"14686","DOI":"10.1038\/s41598-022-18512-1","article-title":"Osteogenic Transdifferentiation of Primary Human Fibroblasts to Osteoblast-like Cells with Human Platelet Lysate","volume":"12","author":"Cayami","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2836","DOI":"10.1080\/15384101.2020.1827188","article-title":"Promoting Effect of Long Non-Coding RNA SNHG1 on Osteogenic Differentiation of Fibroblastic Cells from the Posterior Longitudinal Ligament by the microRNA-320b\/IFNGR1 Network","volume":"19","author":"Wang","year":"2020","journal-title":"Cell Cycle"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1007\/s00223-019-00608-y","article-title":"Long Non-Coding RNA XIST May Influence Cervical Ossification of the Posterior Longitudinal Ligament Through Regulation of miR-17-5P\/AHNAK\/BMP2 Signaling Pathway","volume":"105","author":"Liao","year":"2019","journal-title":"Calcif. Tissue Int."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s10048-017-0520-x","article-title":"X-Linked Hypomyelination with Spondylometaphyseal Dysplasia (H-SMD) Associated with Mutations in AIFM1","volume":"18","author":"Miyake","year":"2017","journal-title":"Neurogenetics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1056\/NEJMc2214862","article-title":"Safety and Efficacy of Denosumab for Fibrous Dysplasia of Bone","volume":"388","author":"Michel","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_36","first-page":"247","article-title":"Effects of Zoledronic Acid Therapy in Fibrous Dysplasia of Bone: A Single-Center Experience","volume":"66","author":"Valadares","year":"2022","journal-title":"Arch. Endocrinol. Metab."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.steroids.2013.10.019","article-title":"New Insights on Membrane Mediated Effects of 1\u03b1,25-Dihydroxy Vitamin D3 Signaling in the Musculoskeletal System","volume":"81","author":"Doroudi","year":"2014","journal-title":"Steroids"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/9\/4954\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:38:12Z","timestamp":1760107092000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/9\/4954"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,1]]},"references-count":37,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["ijms25094954"],"URL":"https:\/\/doi.org\/10.3390\/ijms25094954","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,1]]}}}