{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T01:24:49Z","timestamp":1779931489149,"version":"3.53.1"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T00:00:00Z","timestamp":1739836800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Rakuno Gakuen Univ.","award":["Rakuno Gakuen Univ. Research Fund (2024-02)"],"award-info":[{"award-number":["Rakuno Gakuen Univ. Research Fund (2024-02)"]}]},{"name":"Rakuno Gakuen Univ.","award":["Rakuno Gakuen Univ. Research Fund (2024-02)"],"award-info":[{"award-number":["Rakuno Gakuen Univ. Research Fund (2024-02)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Collagen fibrils in the dermis are bundled by glycosaminoglycan (GAG) chains of decorin, which contribute to its strength. The three-dimensional structure of collagen fibrils and GAG chains has been discussed on the basis of observations and experiments. This study uses scanning transmission electron microscope (STEM) tomography with high Z-axis resolution to analyze the three-dimensional structure of GAG chains in the dermis from a healthy individual and a patient with musculocontractural Ehlers\u2013Danlos syndrome caused by pathogenic variants in CHST14 (mcEDS-CHST14). This observation revealed that the dermis from a healthy individual featured multiple GAG chains that wrapped around collagen fibrils and formed incomplete ring structures. However, in the dermis from a patient with mcEDS-CHST14, GAG chains were linear and did not form rings. Based on the relationship between collagen fibrils and GAG chains, we suggest the three-dimensional structure of normal GAG chains in a new model named the \u2018segmented ring-mesh model\u2019. The interactions between collagen fibrils and GAG chains in this model also apply to the dermis of mcEDS-CHST14 patients, in which the GAG chain composition changes to become CS-rich and more linear. This change leads to an increased inter-fibrillar space, which inhibits the dense packing of collagen fibrils. These findings suggest that this phenomenon contributes to the skin fragility observed in mcEDS-CHST14 patients. Our study suggests the \u2018segmented ring-mesh model\u2019 of GAG chains is essential for the dense packing of collagen fibrils in normal dermis. STEM tomography is highly effective in analyzing the three-dimensional structure of collagen fibrils and GAG chains.<\/jats:p>","DOI":"10.1093\/jmicro\/dfaf012","type":"journal-article","created":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T06:32:46Z","timestamp":1739860366000},"page":"358-366","source":"Crossref","is-referenced-by-count":1,"title":["Segmented ring-mesh model of glycosaminoglycan chains based on the 3D analysis of normal individual and musculocontractural Ehlers\u2013Danlos syndrome skin using scanning transmission electron microscopy"],"prefix":"10.1093","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8531-9448","authenticated-orcid":false,"given":"Naoki","family":"Takahashi","sequence":"first","affiliation":[{"name":"Laboratory of Veterinary Anatomy, Department of Veterinary Medicine, School of Veterinary Medicine, Rakuno Gakuen University , 582 Bunkyodai Midori-machi, Ebetsu City, Hokkaido 069-8501,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Hirose","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Anatomy, Department of Veterinary Medicine, School of Veterinary Medicine, Rakuno Gakuen University , 582 Bunkyodai Midori-machi, Ebetsu City, Hokkaido 069-8501,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyokazu","family":"Kametani","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Anatomy, Department of Veterinary Medicine, School of Veterinary Medicine, Rakuno Gakuen University , 582 Bunkyodai Midori-machi, Ebetsu City, Hokkaido 069-8501,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohito","family":"Iwasaki","sequence":"additional","affiliation":[{"name":"Laboratory of Meat Science, Department of Food Science and Human Wellness, College of Agriculture, Food and Environment, Rakuno Gakuen University , 582 Bunkyodai Midori-machi, Ebetsu City, Hokkaido 069-8501,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6264-1709","authenticated-orcid":false,"given":"Yasutada","family":"Imamura","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Life Science, School of Advanced Engineering, Kogakuin University , 2665-1 Nakano-machi Hachioji City, Tokyo 192-0015,","place":["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":"Center for Medical Genetics, Shinshu University Hospital , 3-1-1 Asahi, Matsumoto Nagano, Nagano 390-8621,","place":["Japan"]},{"name":"Department of Medical Genetics, Shinshu University School of Medicine , 3-1-1 Asahi, Matsumoto Nagano, Nagano 390-8621,","place":["Japan"]},{"name":"Division of Clinical Sequencing, Shinshu University School of Medicine , 3-1-1 Asahi, Matsumoto Nagano, Nagano 390-8621,","place":["Japan"]},{"name":"Research Center for Advanced Science and Technology, Shinshu University , 3-1-1 Asahi, Matsumoto Nagano, Nagano 390-8621,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takafumi","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Anatomy, Department of Veterinary Medicine, School of Veterinary Medicine, Rakuno Gakuen University , 582 Bunkyodai Midori-machi, Ebetsu City, Hokkaido 069-8501,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,2,18]]},"reference":[{"key":"2025101515591796000_R1","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1111\/iep.12224","article-title":"Fell Muir Lecture: collagen fibril formation in vitro and in vivo","volume":"98","author":"Kadler","year":"2017","journal-title":"Int. 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