{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T01:38:17Z","timestamp":1791509897031,"version":"4.3.4"},"reference-count":74,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T00:00:00Z","timestamp":1645574400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R15HD090603"],"award-info":[{"award-number":["R15HD090603"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R15HD090603"],"award-info":[{"award-number":["R15HD090603"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Bone abnormalities affect all individuals with Down syndrome (DS) and are linked to abnormal expression of <jats:italic>DYRK1A<\/jats:italic>, a gene found in three copies in people with DS and Ts65Dn DS model mice. Previous work in Ts65Dn male mice demonstrated that both genetic normalization of <jats:italic>Dyrk1a<\/jats:italic> and treatment with ~9 mg\/kg\/day Epigallocatechin-3-gallate (EGCG), the main polyphenol found in green tea and putative DYRK1A inhibitor, improved some skeletal deficits. Because EGCG treatment improved mostly trabecular skeletal deficits, we hypothesized that increasing EGCG treatment dosage and length of administration would positively affect both trabecular and cortical bone in Ts65Dn mice. Treatment of individuals with DS with green tea extract (GTE) containing EGCG also showed some weight loss in individuals with DS, and we hypothesized that weights would be affected in Ts65Dn mice after EGCG treatment. Treatment with ~20 mg\/kg\/day EGCG for seven weeks showed no improvements in male Ts65Dn trabecular bone and only limited improvements in cortical measures. Comparing skeletal analyses after ~20mg\/kg\/day EGCG treatment with previously published treatments with ~9, 50, and 200 mg\/kg\/day EGCG showed that increased dosage and treatment time increased cortical structural deficits leading to weaker appendicular bones in male mice. Weight was not affected by treatment in mice, except for those given a high dose of EGCG by oral gavage. These data indicate that high doses of EGCG, similar to those reported in some treatment studies of DS and other disorders, may impair long bone structure and strength. Skeletal phenotypes should be monitored when high doses of EGCG are administered therapeutically.<\/jats:p>","DOI":"10.1371\/journal.pone.0264254","type":"journal-article","created":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T18:35:54Z","timestamp":1645641354000},"page":"e0264254","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":24,"title":["Increased dosage and treatment time of Epigallocatechin-3-gallate (EGCG) negatively affects skeletal parameters in normal mice and Down syndrome mouse models"],"prefix":"10.1371","volume":"17","author":[{"given":"Raza","family":"Jamal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"LaCombe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roshni","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Blackwell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared R.","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kourtney","family":"Sloan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph M.","family":"Wallace","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9860-5037","authenticated-orcid":true,"given":"Randall J.","family":"Roper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,2,23]]},"reference":[{"issue":"4","key":"pone.0264254.ref001","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1007\/s003300050726","article-title":"Bone mineral density in adults with Down\u2019s syndrome","volume":"9","author":"N Angelopoulou","year":"1999","journal-title":"Eur Radiol"},{"key":"pone.0264254.ref002","article-title":"Bone Mineral Density Distribution Curves in Spanish Adults With Down Syndrome","author":"R Costa","year":"2018","journal-title":"J Clin Densitom"},{"issue":"3","key":"pone.0264254.ref003","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1111\/j.1754-4505.2008.00020.x","article-title":"Skeletal age of individuals with Down syndrome.","volume":"28","author":"ME de Moraes","year":"2008","journal-title":"Special care in dentistry: official publication of the American Association of Hospital Dentists, the Academy of Dentistry for the Handicapped, and the American Society for Geriatric Dentistry"},{"issue":"2","key":"pone.0264254.ref004","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1136\/adc.87.2.97","article-title":"Growth charts for Down\u2019s syndrome from birth to 18 years of age","volume":"87","author":"A Myrelid","year":"2002","journal-title":"Arch Dis Child"},{"issue":"10","key":"pone.0264254.ref005","doi-asserted-by":"crossref","first-page":"2929","DOI":"10.1007\/s00198-017-4133-x","article-title":"Bone mineral density in adults with Down syndrome","volume":"28","author":"A Carfi","year":"2017","journal-title":"Osteoporos Int"},{"key":"pone.0264254.ref006","article-title":"Bone mineral density from early to middle adulthood in persons with Down syndrome","author":"JYM Tang","year":"2019","journal-title":"J Intellect Disabil Res"},{"key":"pone.0264254.ref007","doi-asserted-by":"crossref","first-page":"115215","DOI":"10.1016\/j.bone.2019.115215","article-title":"Skeletal dynamics of Down syndrome: A developing perspective","volume":"133","author":"JM LaCombe","year":"2020","journal-title":"Bone"},{"key":"pone.0264254.ref008","doi-asserted-by":"crossref","first-page":"115367","DOI":"10.1016\/j.bone.2020.115367","article-title":"Interaction of sexual dimorphism and gene dosage imbalance in skeletal deficits associated with Down syndrome","volume":"136","author":"JR Thomas","year":"2020","journal-title":"Bone"},{"key":"pone.0264254.ref009","article-title":"Current Analysis of Skeletal Phenotypes in Down Syndrome.","author":"JR Thomas","year":"2021","journal-title":"Current osteoporosis reports."},{"issue":"5","key":"pone.0264254.ref010","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1111\/jar.12438","article-title":"50 years with Down syndrome: A longitudinal study.","volume":"31","author":"J Carr","year":"2018","journal-title":"J Appl Res Intellect Disabil"},{"issue":"12","key":"pone.0264254.ref011","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1007\/s00431-010-1253-0","article-title":"Clinical practice. 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