{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T09:05:25Z","timestamp":1784192725118,"version":"3.55.0"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"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":"crossref","award":["2022-02449"],"award-info":[{"award-number":["2022-02449"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"crossref","award":["2019-01919"],"award-info":[{"award-number":["2019-01919"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100018713","name":"CIMED","doi-asserted-by":"crossref","award":["FoUI-976434"],"award-info":[{"award-number":["FoUI-976434"]}],"id":[{"id":"10.13039\/501100018713","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004047","name":"Karolinska Institutet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004047","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Foundation","doi-asserted-by":"crossref","award":["0067241"],"award-info":[{"award-number":["0067241"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004047","name":"Karolinska Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004047","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Biol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Longitudinal bone growth occurs via endochondral ossification, involving a complex interplay of chondrocyte proliferation, differentiation, and matrix remodeling. As with all mammalian cells, chondrocytes require dynamin for mitochondrial fission, to shuttle vesicles from the Golgi apparatus, and for both clathrin- and caveolin-mediated endocytosis. Here, we aimed to test the functions of dynamin on bone growth. To do so, we applied dynasore\u2014a small molecule that is a reversible dynamin inhibitor\u2014to mouse metatarsal bones cultured ex vivo. We assessed gross changes using bone length measurements combined with EdU detection, immunostaining, super-resolution microscopy and transmission electron microscopy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Dynasore induced a dose-dependent hormetic effect on bone elongation: while high concentrations (220\u00a0\u00b5M) impaired growth and abolished chondrocyte proliferation, low-dose treatment (40\u00a0\u00b5M) significantly increased longitudinal bone growth. Histological analysis demonstrated that low dose dynasore augmented epiphyseal cartilage expansion and matrix accumulation, while reducing chondrocyte proliferation. Immunostaining indicated that 40\u00a0\u00b5M dynasore preserved collagen type X synthesis, activated mTORC1 signaling, and blocked autophagy, based on SQSTM1 accumulation. Low dose dynasore treatment expanded the thickness of the filamentous actin layer at the plasma membrane and deepened endocytic pits containing collagen fibril-like electron-dense extracellular structures, indicating that impaired cartilage remodeling was associated with growth-associated matrix accumulation. Finally, the use of a structurally unrelated dynamin inhibitor, dynole, indicated that the effects of dynasore were partially mediated by its actions on dynamin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Dynasore exerts hormetic effects on epiphyseal chondrocytes, wherein low doses stimulate bone elongation, and high doses impair chondrocyte function.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12915-026-02687-4","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T06:04:37Z","timestamp":1784181877000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dynamin inhibitor dynasore modulates longitudinal bone growth in a hormetic manner"],"prefix":"10.1186","volume":"24","author":[{"given":"Jose G.","family":"Marchan-Alvarez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanya","family":"Koikkara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruihan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal","family":"Nazaraliyev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar P. B.","family":"Wiklander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip T.","family":"Newton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"key":"2687_CR1","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1038\/s41390-019-0722-z","volume":"87","author":"AS Chagin","year":"2020","unstructured":"Chagin AS, Newton PT. Postnatal skeletal growth is driven by the epiphyseal stem cell niche: potential implications to pediatrics. Pediatr Res. 2020;87:986\u201390. https:\/\/doi.org\/10.1038\/s41390-019-0722-z.","journal-title":"Pediatr Res"},{"key":"2687_CR2","doi-asserted-by":"publisher","first-page":"15021","DOI":"10.1038\/boneres.2015.21","volume":"3","author":"A Kohn","year":"2015","unstructured":"Kohn A, Rutkowski TP, Liu Z, Mirando AJ, Zuscik MJ, O\u2019Keefe RJ, et al. 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The animals were purchased from Charles River (strain code: 632). Mice were group-housed with the parent mouse on a 12\u00a0h light\u2013dark cycle at 22\u00a0\u00b0C with 50% humidity and weaned on postnatal day 21, and then housed with siblings of the same sex. Breeding was performed in-house and litters collected for metatarsal isolation on postnatal day three. All procedures were performed by certified personnel at the Comparative Medicine Biomedicum (Komparativ Medicin Biomedicum, KM-B), a dedicated facility for research on small rodents, at Karolinska Institutet.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Oscar P.B. Wiklander has a financial interest in Evox Therapeutics.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"169"}}