{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T01:26:18Z","timestamp":1779931578516,"version":"3.53.1"},"reference-count":44,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,16]],"date-time":"2023-03-16T00:00:00Z","timestamp":1678924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Grants-in-Aid for Scientific Research (C)","award":["21K0924600"],"award-info":[{"award-number":["21K0924600"]}]},{"name":"Grants-in-Aid for Scientific Research (C)","award":["19H0361604"],"award-info":[{"award-number":["19H0361604"]}]},{"name":"Grants-in-Aid for Scientific Research (C)","award":["19H03616"],"award-info":[{"award-number":["19H03616"]}]},{"name":"Grants-in-Aid for Scientific Research (C)","award":["22bm0804019h0003"],"award-info":[{"award-number":["22bm0804019h0003"]}]},{"name":"Grants-in-Aid for Scientific Research (B)","award":["21K0924600"],"award-info":[{"award-number":["21K0924600"]}]},{"name":"Grants-in-Aid for Scientific Research (B)","award":["19H0361604"],"award-info":[{"award-number":["19H0361604"]}]},{"name":"Grants-in-Aid for Scientific Research (B)","award":["19H03616"],"award-info":[{"award-number":["19H03616"]}]},{"name":"Grants-in-Aid for Scientific Research (B)","award":["22bm0804019h0003"],"award-info":[{"award-number":["22bm0804019h0003"]}]},{"name":"the Acceleration Program for Intractable Diseases Research utilizing Disease-specific iPSCs","award":["21K0924600"],"award-info":[{"award-number":["21K0924600"]}]},{"name":"the Acceleration Program for Intractable Diseases Research utilizing Disease-specific iPSCs","award":["19H0361604"],"award-info":[{"award-number":["19H0361604"]}]},{"name":"the Acceleration Program for Intractable Diseases Research utilizing Disease-specific iPSCs","award":["19H03616"],"award-info":[{"award-number":["19H03616"]}]},{"name":"the Acceleration Program for Intractable Diseases Research utilizing Disease-specific iPSCs","award":["22bm0804019h0003"],"award-info":[{"award-number":["22bm0804019h0003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Musculocontractural Ehlers\u2013Danlos syndrome caused by mutations in the carbohydrate sulfotransferase 14 gene (mcEDS-CHST14) is a heritable connective tissue disorder characterized by multiple congenital malformations and progressive connective tissue fragility-related manifestations in the cutaneous, skeletal, cardiovascular, visceral, and ocular systems. Progressive skeletal deformities are among the most frequent and serious complications affecting the quality of life and activities of daily living in patients. After establishing induced pluripotent stem cells (iPSCs) from cultured skin fibroblasts of three patients with mcEDS-CHST14, we generated a patient iPSC-based human osteogenesis model and performed an in vitro assessment of the phenotype and pathophysiology of skeletal deformities. Patient-derived iPSCs presented with remarkable downregulation of osteogenic-specific gene expression, less alizarin red staining, and reduced calcium deposition compared with wild-type iPSCs at each stage of osteogenic differentiation, including osteoprogenitor cells, osteoblasts, and osteocytes. These findings indicated that osteogenesis was impaired in mcEDS-CHST14 iPSCs. Moreover, the decrease in decorin (DCN) expression and increase in collagen (COL12A1) expression in patient-derived iPSCs elucidated the contribution of CHST14 dysfunction to skeletal deformities in mcEDS-CHST14. In conclusion, this disease-in-a-dish model provides new insight into the pathophysiology of EDS and may have the potential for personalized gene or drug therapy.<\/jats:p>","DOI":"10.3390\/genes14030730","type":"journal-article","created":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T04:10:48Z","timestamp":1679026248000},"page":"730","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Pathophysiological Investigation of Skeletal Deformities of Musculocontractural Ehlers\u2013Danlos Syndrome Using Induced Pluripotent Stem Cells"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7941-0675","authenticated-orcid":false,"given":"Fengming","family":"Yue","sequence":"first","affiliation":[{"name":"Department of Histology and Embryology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan"},{"name":"Shinshu University Interdisciplinary Cluster for Cutting Edge Research, Institute for Biomedical Sciences, Matsumoto 390-8621, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takumi","family":"Era","sequence":"additional","affiliation":[{"name":"Department of Cell Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0811, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomomi","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto 390-8621, Japan"},{"name":"Center for Medical Genetics, Shinshu University Hospital, Matsumoto 390-8621, Japan"},{"name":"Division of Clinical Sequencing, Shinshu University School of Medicine, Matsumoto 390-8621, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8344-7507","authenticated-orcid":false,"given":"Tomoki","family":"Kosho","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto 390-8621, Japan"},{"name":"Center for Medical Genetics, Shinshu University Hospital, Matsumoto 390-8621, Japan"},{"name":"Division of Clinical Sequencing, Shinshu University School of Medicine, Matsumoto 390-8621, Japan"},{"name":"Research Center for Supports to Advanced Science, Shinshu University, Matsumoto 390-8621, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,16]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"The Ehlers-Danlos syndromes","volume":"6","author":"Malfait","year":"2020","journal-title":"Nat. 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