{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T06:36:12Z","timestamp":1773902172523,"version":"3.50.1"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T00:00:00Z","timestamp":1725926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21 AG078861-01"],"award-info":[{"award-number":["R21 AG078861-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Veterans Research Administration Merit Award","award":["I01BX005154"],"award-info":[{"award-number":["I01BX005154"]}]},{"name":"Research Support Funds Grant"},{"name":"Office of the Vice Chancellor for Research at Indiana University Purdue University Indianapolis"},{"name":"NIH\/NIGMS","award":["R25-GM109432"],"award-info":[{"award-number":["R25-GM109432"]}]},{"name":"Becas de Movilidad con Perspectiva de G\u00e9nero","award":["BMG-2023-115"],"award-info":[{"award-number":["BMG-2023-115"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,10,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Vertebrate sexual dimorphism is ascribed to the presence of testes or ovaries, and, hence, to the secretion of gonad-specific hormones. However, mounting evidence indicates that sex differences in tissues and organs also stem from the presence of sex chromosomes (XX or XY). To tease out the contribution of gonads from sex chromosomes to the musculoskeletal system, we used the Four-Core Genotypes (FCG) mouse model, in which the Sry gene, which dictates testis formation, was either deleted from the Y chromosome, resulting in XY mice with ovaries (XY-SryO), or overexpressed in XX mice, resulting in XX mice with testes (XXT), together with gonadal males with XY-SryT (Sry deletion and overexpression of the Sry transgene in chromosome 3) and females with XXO. The FCG mice are generated by crossing XXO with XY-SryT mice, all of C57BL\/6\u00a0J background. We now show that the musculoskeletal phenotype of 2- to 4-mo-old FCG mice varies based on both gonads and sex chromosomes, depending on the age and the organ\/tissue\/cell analyzed. The effect of sex chromosomes on body weight, fat and lean\/skeletal muscle mass, and bone mass and structure is minor in 2-\/3-mo-old mice, soon after sexual maturation. The contribution of sex chromosomes (XX vs XY-Sry in mice with the same gonads and sex hormones) to several of our measurements becomes apparent in adult 4-mo-old mice. The contribution of 1X and 1Y-Sry vs 2X chromosomes varies among different measurements in gonadal males or females, and mice with XY-Sry chromosomes might have higher or lower values that XX mice. Our study shows XX vs XY-Sry chromosome contribution to the musculoskeletal phenotype, which becomes more evident as the animals reach peak bone mass, suggesting that although gonadal sex has a major role, sex chromosomes are also an unrecognized contributor to musculoskeletal mass and bone strength.<\/jats:p>","DOI":"10.1093\/jbmr\/zjae147","type":"journal-article","created":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T03:40:42Z","timestamp":1725939642000},"page":"1659-1672","source":"Crossref","is-referenced-by-count":7,"title":["Independent contribution of gonads and sex chromosomes to sex differences in bone mass and strength in the four-core genotypes mouse model"],"prefix":"10.1093","volume":"39","author":[{"given":"Gabriel","family":"Ramirez","sequence":"first","affiliation":[{"name":"Department of Anatomy , Cell Biology & Physiology, , Indianapolis, IN 46202,","place":["United States"]},{"name":"Indiana University School of Medicine , Cell Biology & Physiology, , Indianapolis, IN 46202,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiebuka","family":"Okpara","sequence":"additional","affiliation":[{"name":"Department of Anatomy , Cell Biology & Physiology, , Indianapolis, IN 46202,","place":["United States"]},{"name":"Indiana University School of Medicine , Cell Biology & Physiology, , Indianapolis, IN 46202,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Arnett","sequence":"additional","affiliation":[{"name":"Department of Anatomy , Cell Biology & Physiology, , Indianapolis, IN 46202,","place":["United States"]},{"name":"Indiana University School of Medicine , Cell Biology & Physiology, , Indianapolis, IN 46202,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dyann M","family":"Segvich","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering , Weldon School of Biomedical Engineering, , West Lafayette, IN 47907,","place":["United States"]},{"name":"Purdue University , Weldon School of Biomedical Engineering, , West Lafayette, IN 47907,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Padmini","family":"Deosthale","sequence":"additional","affiliation":[{"name":"Department of Anatomy , Cell Biology & Physiology, , Indianapolis, IN 46202,","place":["United States"]},{"name":"Indiana University School of Medicine , Cell Biology & Physiology, , Indianapolis, IN 46202,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola Ortiz","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Department of Anatomy , Cell Biology & Physiology, , Indianapolis, IN 46202,","place":["United States"]},{"name":"Indiana University School of Medicine , Cell Biology & Physiology, , Indianapolis, IN 46202,","place":["United States"]},{"name":"Indiana Center for Musculoskeletal Health , Indiana University School of Medicine, Indianapolis, IN 46202,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander E","family":"Kritikos","sequence":"additional","affiliation":[{"name":"Department of Anatomy , Cell Biology & Physiology, , Indianapolis, IN 46202,","place":["United States"]},{"name":"Indiana University School of Medicine , Cell Biology & Physiology, , Indianapolis, IN 46202,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julian Balanta","family":"Melo","sequence":"additional","affiliation":[{"name":"Department of Anatomy , Cell Biology & Physiology, , Indianapolis, IN 46202,","place":["United States"]},{"name":"Indiana University School of Medicine , Cell Biology & Physiology, , Indianapolis, IN 46202,","place":["United States"]},{"name":"Dentistry Unit, Universidad del Valle School of Dentistry , Cali, Valle de Cauca 760042,","place":["Colombia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natasha","family":"Sanz","sequence":"additional","affiliation":[{"name":"Department of Anatomy , Cell Biology & Physiology, , Indianapolis, IN 46202,","place":["United States"]},{"name":"Indiana University School of Medicine , Cell Biology & Physiology, , Indianapolis, IN 46202,","place":["United States"]},{"name":"Bone Biology Laboratory. School of Medicine, Rosario National University, Rosario , Santa Fe 2000,","place":["Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabrizio","family":"Pin","sequence":"additional","affiliation":[{"name":"Department of Anatomy , Cell Biology & Physiology, , Indianapolis, IN 46202,","place":["United States"]},{"name":"Indiana University School of Medicine , Cell Biology & Physiology, , Indianapolis, IN 46202,","place":["United States"]},{"name":"Indiana Center for Musculoskeletal Health , Indiana University School of Medicine, Indianapolis, IN 46202,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph M","family":"Wallace","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering , Weldon School of Biomedical Engineering, , West Lafayette, IN 47907,","place":["United States"]},{"name":"Purdue University , Weldon School of Biomedical Engineering, , West Lafayette, IN 47907,","place":["United States"]},{"name":"Indiana Center for Musculoskeletal Health , Indiana University School of Medicine, Indianapolis, IN 46202,","place":["United States"]},{"name":"Roudebush Veterans Administration Medical Center , Indianapolis, IN 46202,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9537-4544","authenticated-orcid":false,"given":"Lilian I","family":"Plotkin","sequence":"additional","affiliation":[{"name":"Department of Anatomy , Cell Biology & Physiology, , Indianapolis, IN 46202,","place":["United States"]},{"name":"Indiana University School of Medicine , Cell Biology & Physiology, , Indianapolis, IN 46202,","place":["United States"]},{"name":"Indiana Center for Musculoskeletal Health , Indiana University School of Medicine, Indianapolis, IN 46202,","place":["United States"]},{"name":"Roudebush Veterans Administration Medical Center , Indianapolis, IN 46202,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,9,10]]},"reference":[{"issue":"10","key":"2024103012172241400_ref1","doi-asserted-by":"publisher","first-page":"2304","DOI":"10.1002\/jcp.24979","article-title":"Genetic architecture of sexual dimorphism in humans","volume":"230","author":"Rigby","year":"2015","journal-title":"J Cell Physiol"},{"issue":"1","key":"2024103012172241400_ref2","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1152\/physrev.00033.2015","article-title":"Estrogens and androgens in skeletal physiology and pathophysiology","volume":"97","author":"Almeida","year":"2017","journal-title":"Physiol Rev"},{"issue":"1","key":"2024103012172241400_ref3","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1152\/physrev.2001.81.1.419","article-title":"Sex steroids and bone","volume":"81","author":"Compston","year":"2001","journal-title":"Physiol Rev"},{"issue":"2","key":"2024103012172241400_ref4","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/j.kint.2018.03.021","article-title":"Bones and the sex hormones","volume":"94","author":"Narla","year":"2018","journal-title":"Kidney Int"},{"key":"2024103012172241400_ref5","doi-asserted-by":"publisher","first-page":"100926","DOI":"10.1016\/j.yfrne.2021.100926","article-title":"On the role of sex steroids in biological functions by classical and non-classical pathways. 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