{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T08:28:17Z","timestamp":1786436897839,"version":"build-2736575974"},"reference-count":20,"publisher":"The Endocrine Society","issue":"9","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["2021-01807"],"award-info":[{"award-number":["2021-01807"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003849","name":"IngaBritt och Arne Lundbergs forskningsstiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003849","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011727","name":"Stockholm County Council","doi-asserted-by":"publisher","award":["2024-0781"],"award-info":[{"award-number":["2024-0781"]}],"id":[{"id":"10.13039\/501100011727","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009747","name":"Erik and Edith Fernstr\u00f6m Foundation for Medical Research, Promobilia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009747","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012280","name":"Swedish Rare Diseases Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012280","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020325","name":"S\u00e4llskapet Barnav\u00e5rd","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020325","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009810","name":"Wera Ekstr\u00f6m\u2019s Foundation for Pediatric Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009810","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006741","name":"Stiftelsen Frimurare Barnhuset i Stockholm","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006741","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004047","name":"Karolinska Institutet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004047","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In growing children, estrogen accelerates skeletal maturation, leading to advanced bone age, earlier growth cessation, and epiphyseal fusion. Children with heterozygous pathogenic variants in the aggrecan gene (ACAN) typically exhibit postnatal growth failure, advanced bone age, and premature growth cessation. To investigate whether accelerated skeletal maturation in aggrecan deficiency reflects increased sensitivity to estrogen-induced growth plate senescence, we used a mouse model carrying a heterozygous truncating variant in Acan (Acan+\/\u2212). Consistent with the human phenotype, these mice display postnatal growth failure and early growth cessation. Seven-week-old ovariectomized (OVX) wild-type and Acan+\/\u2212 mice received weekly estradiol cypionate (0.15\u2005\u00b5g\/g) or vehicle treatment for 4 weeks. As expected, OVX reduced and estradiol increased uterine weights in both genotypes. In wild-type mice, estradiol treatment significantly reduced tibial growth and several structural markers of growth plate function. In Acan+\/\u2212 mice, fewer parameters were significantly affected by estradiol treatment. Importantly, we found no evidence that aggrecan deficiency increases susceptibility to estrogen-induced growth plate senescence. These findings challenge the hypothesis that accelerated skeletal maturation in ACAN deficiency reflects heightened estrogen sensitivity and instead point to intrinsic abnormalities of growth plate cartilage as a driver of premature growth cessation.<\/jats:p>","DOI":"10.1210\/jendso\/bvag163","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T11:35:10Z","timestamp":1784633710000},"source":"Crossref","is-referenced-by-count":0,"title":["Aggrecan deficiency does not increase susceptibility to estrogen-induced growth plate senescence"],"prefix":"10.1210","volume":"10","author":[{"given":"Ameya","family":"Bendre","sequence":"first","affiliation":[{"name":"Division of Pediatric Endocrinology and Center for Molecular Medicine, Department of Women's and Children's Health, Karolinska Institutet , Stockholm SE-171 76 ,","place":["Sweden"]},{"name":"Department of Pediatric Endocrinology, Astrid Lindgren Children's Hospital, Karolinska University Hospital , Stockholm SE-171 76 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6446-3643","authenticated-orcid":false,"given":"Henrique","family":"Hadad","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology and Center for Molecular Medicine, Department of Women's and Children's Health, Karolinska Institutet , Stockholm SE-171 76 ,","place":["Sweden"]},{"name":"Department of Pediatric Endocrinology, Astrid Lindgren Children's Hospital, Karolinska University Hospital , Stockholm SE-171 76 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2488-6403","authenticated-orcid":false,"given":"Lars","family":"Ottosson","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology and Center for Molecular Medicine, Department of Women's and Children's Health, Karolinska Institutet , Stockholm SE-171 76 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