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Our previous study showed that low doses of green tea extract enriched in epigallocatechin-3-gallate (GTE-EGCG), administered continuously from embryonic day 9 to postnatal day 29, reduced facial dysmorphologies in the Ts65Dn (TS) mouse model of DS, but high doses could exacerbate them. Here, we extended the analyses to other skeletal structures and systematically evaluated the effects of high and low doses of GTE-EGCG treatment over postnatal development in wild-type (WT) and TS mice using in vivo \u00b5CT and geometric morphometrics. TS mice developed shorter and wider faces, skulls, and mandibles, together with shorter and narrower humerus and scapula, and reduced BMD dynamically over time. Besides facial morphology, GTE-EGCG did not rescue any other skeletal phenotype in TS treated mice. In WT mice, GTE-EGCG significantly altered the shape of the skull and mandible, reduced the length and width of the long bones, and lowered the BMD. The disparate effects of GTE-EGCG depended on the dose, developmental timepoint, and anatomical structure analyzed, emphasizing the complex nature of DS and the need to further investigate the simultaneous effects of GTE-EGCG supplementation.<\/jats:p>","DOI":"10.3390\/nu14194167","type":"journal-article","created":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T01:21:07Z","timestamp":1665364867000},"page":"4167","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Green Tea Catechins Modulate Skeletal Development with Effects Dependent on Dose, Time, and Structure in a down Syndrome Mouse Model"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9980-0208","authenticated-orcid":false,"given":"Sergi","family":"Llambrich","sequence":"first","affiliation":[{"name":"Biomedical MRI, Department of Imaging and Pathology, University of Leuven (KU Leuven), 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rub\u00e8n","family":"Gonz\u00e1lez-Colom","sequence":"additional","affiliation":[{"name":"Departament de Biologia Evolutiva, Ecologia i Ci\u00e8ncies Ambientals (BEECA), Facultat de Biologia, Universitat de Barcelona (UB), 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Wouters","sequence":"additional","affiliation":[{"name":"Biomedical MRI, Department of Imaging and Pathology, University of Leuven (KU Leuven), 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9591-3555","authenticated-orcid":false,"given":"Jorge","family":"Rold\u00e1n","sequence":"additional","affiliation":[{"name":"Departament de Biologia Evolutiva, Ecologia i Ci\u00e8ncies Ambientals (BEECA), Facultat de Biologia, Universitat de Barcelona (UB), 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Salassa","sequence":"additional","affiliation":[{"name":"Departament de Biologia Evolutiva, Ecologia i Ci\u00e8ncies Ambientals (BEECA), Facultat de Biologia, Universitat de Barcelona (UB), 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaat","family":"Wouters","sequence":"additional","affiliation":[{"name":"Laboratory of Biological Psychology, University of Leuven (KU Leuven), 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9355-0567","authenticated-orcid":false,"given":"Vicky","family":"Van Bulck","sequence":"additional","affiliation":[{"name":"Laboratory of Biological Psychology, University of Leuven (KU Leuven), 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Sharpe","sequence":"additional","affiliation":[{"name":"Center for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), 08003 Barcelona, Spain"},{"name":"Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain"},{"name":"Instituci\u00f3 Catalana de Recerca i Estudis Avan\u00e7ats (ICREA), 08003 Barcelona, Spain"},{"name":"EMBL Barcelona, European Molecular Biology Laboratory, 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsuzsanna","family":"Callaerts-Vegh","sequence":"additional","affiliation":[{"name":"Laboratory of Biological Psychology, University of Leuven (KU Leuven), 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5633-3993","authenticated-orcid":false,"given":"Greetje","family":"Vande Velde","sequence":"additional","affiliation":[{"name":"Biomedical MRI, Department of Imaging and Pathology, University of Leuven (KU Leuven), 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3061-2123","authenticated-orcid":false,"given":"Neus","family":"Mart\u00ednez-Abad\u00edas","sequence":"additional","affiliation":[{"name":"Departament de Biologia Evolutiva, Ecologia i Ci\u00e8ncies Ambientals (BEECA), Facultat de Biologia, Universitat de Barcelona (UB), 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Roper, R.J., and Reeves, R.H. 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