{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T08:50:00Z","timestamp":1765961400260,"version":"build-2065373602"},"reference-count":48,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,16]],"date-time":"2021-05-16T00:00:00Z","timestamp":1621123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/50006\/2020","2020.04935.BD"],"award-info":[{"award-number":["UIDB\/50006\/2020","2020.04935.BD"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["#2015\/03965-2","#2017\/19227-6","#2018\/23934-2"],"award-info":[{"award-number":["#2015\/03965-2","#2017\/19227-6","#2018\/23934-2"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Activation of renin\u2013angiotensin system (RAS) plays a role in bone deterioration associated with bone metabolic disorders, via increased Angiotensin II (AngII) targeting Angiotensin II type 1 receptor\/Angiotensin II type 2 receptor (AT1R\/AT2R). Despite the wide data availability, the RAS role remains controversial. This study analyzes the feasibility of using the embryonic chick femur organotypic model to address AngII\/AT1R\/AT2R axis in bone, which is an application not yet considered. Embryonic day-11 femurs were cultured ex vivo for 11 days in three settings: basal conditions, exposure to AngII, and modulation of AngII effects by prior receptor blockade, i.e., AT1R, AT2R, and AT1R + AT2R. Tissue response was evaluated by combining \u00b5CT and histological analysis. Basal-cultured femurs expressed components of RAS, namely ACE, AT1R, AT2R, and MasR (qPCR analysis). Bone formation occurred in the diaphyseal region in all conditions. In basal-cultured femurs, AT1R blocking increased Bone Surface\/Bone Volume (BS\/BV), whereas Bone Volume\/Tissue Volume (BV\/TV) decreased with AT2R or AT1R + AT2R blockade. Exposure to AngII greatly decreased BV\/TV compared to basal conditions. Receptor blockade prior to AngII addition prevented this effect, i.e., AT1R blockade induced BV\/TV, whereas blocking AT2R caused lower BV\/TV increase but greater BS\/BV; AT1R + AT2R blockade also improved BV\/TV. Concluding, the embryonic chick femur model was sensitive to three relevant RAS research setups, proving its usefulness to address AngII\/AT1R\/AT2R axis in bone both in basal and activated conditions.<\/jats:p>","DOI":"10.3390\/ph14050469","type":"journal-article","created":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T02:31:34Z","timestamp":1621218694000},"page":"469","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The Embryonic Chick Femur Organotypic Model as a Tool to Analyze the Angiotensin II Axis on Bone Tissue"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4507-5148","authenticated-orcid":false,"given":"Thais Francini","family":"Garbieri","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Bauru School of Dentistry, University of S\u00e3o Paulo, Bauru, S\u00e3o Paulo 17012-901, Brazil"},{"name":"Laboratory for Bone Metabolism and Regeneration, Faculty of Dental Medicine, University of Porto, 4200-393 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6910-1705","authenticated-orcid":false,"given":"Victor","family":"Martin","sequence":"additional","affiliation":[{"name":"Laboratory for Bone Metabolism and Regeneration, Faculty of Dental Medicine, University of Porto, 4200-393 Porto, Portugal"},{"name":"LAQV\/REQUIMTE, University of Porto, 4160-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0405-3500","authenticated-orcid":false,"given":"Carlos Ferreira","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Bauru School of Dentistry, University of S\u00e3o Paulo, Bauru, S\u00e3o Paulo 17012-901, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5365-2123","authenticated-orcid":false,"given":"Pedro de Sousa","family":"Gomes","sequence":"additional","affiliation":[{"name":"Laboratory for Bone Metabolism and Regeneration, Faculty of Dental Medicine, University of Porto, 4200-393 Porto, Portugal"},{"name":"LAQV\/REQUIMTE, University of Porto, 4160-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9391-9574","authenticated-orcid":false,"given":"Maria Helena","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Laboratory for Bone Metabolism and Regeneration, Faculty of Dental Medicine, University of Porto, 4200-393 Porto, Portugal"},{"name":"LAQV\/REQUIMTE, University of Porto, 4160-007 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,16]]},"reference":[{"doi-asserted-by":"crossref","unstructured":"Tamargo, M., and Tamargo, J. 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