{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:45:14Z","timestamp":1788223514699,"version":"build-2803163510"},"reference-count":43,"publisher":"American Society for Clinical Investigation","issue":"6","license":[{"start":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T00:00:00Z","timestamp":1711065600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"crossref","award":["2020-02298"],"award-info":[{"award-number":["2020-02298"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NovoNordisk Foundation","award":["NNF21OC0070314"],"award-info":[{"award-number":["NNF21OC0070314"]}]},{"name":"ALF-agreement","award":["ALFGBG-966178"],"award-info":[{"award-number":["ALFGBG-966178"]}]},{"name":"the Russian Foundation for Basic Science","award":["19-29-04115"],"award-info":[{"award-number":["19-29-04115"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,22]]},"abstract":"<jats:p>\n                    Recently, skeletal stem cells were shown to be present in the epiphyseal growth plate (epiphyseal skeletal stem cells, epSSCs), but their function in connection with linear bone growth remains unknown. Here, we explore the possibility that modulating the number of epSSCs can correct differences in leg length. First, we examined regulation of the number and activity of epSSCs by Hedgehog (Hh) signaling. Both systemic activation of Hh pathway with Smoothened agonist (SAG) and genetic activation of Hh pathway by Patched1 (\n                    <jats:italic>Ptch1<\/jats:italic>\n                    ) ablation in\n                    <jats:italic>Pthrp-creER<\/jats:italic>\n                    <jats:italic>Ptch1<\/jats:italic>\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    tdTomato mice promoted proliferation of epSSCs and clonal enlargement. Transient intra-articular administration of SAG also elevated the number of epSSCs. When SAG-containing beads were implanted into the femoral secondary ossification center of 1 leg of rats, this leg was significantly longer 1 month later than the contralateral leg implanted with vehicle-containing beads, an effect that was even more pronounced 2 and 6 months after implantation. We conclude that Hh signaling activates growth plate epSSCs, which effectively leads to increased longitudinal growth of bones. This opens therapeutic possibilities for the treatment of differences in leg length.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.165226","type":"journal-article","created":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T09:27:02Z","timestamp":1711445222000},"source":"Crossref","is-referenced-by-count":15,"title":["Stimulation of skeletal stem cells in the growth plate promotes linear bone growth"],"prefix":"10.1172","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9472-6184","authenticated-orcid":true,"given":"Dana","family":"Trompet","sequence":"first","affiliation":[{"name":"Institute of Medicine, Centre for Bone and Arthritis Research at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden."},{"name":"Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6905-9703","authenticated-orcid":true,"given":"Anastasiia D.","family":"Kurenkova","sequence":"additional","affiliation":[{"name":"Institute for Regenerative Medicine, I.M. 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