{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T07:27:05Z","timestamp":1788852425373,"version":"build-2803163510"},"reference-count":46,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,12,30]],"date-time":"2018-12-30T00:00:00Z","timestamp":1546128000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT1049863"],"award-info":[{"award-number":["GNT1049863"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Osteogenesis imperfecta (<jats:styled-content style=\"fixed-case\">OI<\/jats:styled-content>) is commonly caused by heterozygous type I collagen structural mutations that disturb triple helix folding and integrity. This mutant\u2010containing misfolded collagen accumulates in the endoplasmic reticulum (<jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content>) and induces a form of <jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content> stress associated with negative effects on osteoblast differentiation and maturation. Therapeutic induction of autophagy to degrade the mutant collagens could therefore be useful in ameliorating the <jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content> stress and deleterious downstream consequences. To test this, we treated a mouse model of mild to moderate <jats:styled-content style=\"fixed-case\">OI<\/jats:styled-content> (\u03b12(I) G610C) with dietary rapamycin from 3 to 8\u00a0weeks of age and effects on bone mass and mechanical properties were determined. <jats:styled-content style=\"fixed-case\">OI<\/jats:styled-content> bone mass and mechanics were, as previously reported, compromised compared to <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>. While rapamycin treatment improved the trabecular parameters of <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">OI<\/jats:styled-content> bones, the biomechanical deficits of <jats:styled-content style=\"fixed-case\">OI<\/jats:styled-content> bones were not rescued. Importantly, we show that rapamycin treatment suppressed the longitudinal and transverse growth of <jats:styled-content style=\"fixed-case\">OI<\/jats:styled-content>, but not <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>, long bones. Our work demonstrates that dietary rapamycin offers no clinical benefit in this <jats:styled-content style=\"fixed-case\">OI<\/jats:styled-content> model and furthermore, the impact of rapamycin on <jats:styled-content style=\"fixed-case\">OI<\/jats:styled-content> bone growth could exacerbate the clinical consequences during periods of active bone growth in patients with <jats:styled-content style=\"fixed-case\">OI<\/jats:styled-content> caused by collagen misfolding mutations.<\/jats:p>","DOI":"10.1111\/jcmm.14072","type":"journal-article","created":{"date-parts":[[2018,12,31]],"date-time":"2018-12-31T22:29:41Z","timestamp":1546295381000},"page":"1735-1745","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Effect of rapamycin on bone mass and strength in the \u03b12(I)\u2010G610C mouse model of osteogenesis 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