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However, its precise molecular and cellular mechanisms remain unclear. To address this, we aimed to generate knock-in mice (\n                    <jats:italic>Fgfr3<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>Ach<\/jats:italic>\n                    <\/jats:sup>\n                    ) harboring the achondroplasia mutation (p.Gly380Arg). In addition to previously reported abnormalities, we observe an expansion of the resting zone. EdU labeling and lineage tracing analyses indicate that disruption of turnover and impairment of stem cell-like behavior of resting zone chondrocytes results in accumulation of cells in the resting zone. Single-cell RNA-seq and immunohistochemical analysis identify a cell cluster that corresponds to the expanded resting zone. Pathway analysis and functional experiments reveal that CREB disrupts stem cell-like properties in resting zone chondrocytes and contributes to dwarfism. Administration of CREB inhibitor 666-15 restores growth plate pathology and bone length. These findings demonstrate that excess FGFR3 signaling disrupts resting zone chondrocyte properties and suggest potential therapeutic targets for achondroplasia.\n                  <\/jats:p>","DOI":"10.1038\/s41467-026-69507-9","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T10:02:27Z","timestamp":1772100147000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Excess FGFR3 signaling in achondroplasia disrupts turnover of resting zone chondrocytes via CREB signaling"],"prefix":"10.1038","volume":"17","author":[{"given":"Nanao","family":"Horike","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7606-732X","authenticated-orcid":false,"given":"Seiya","family":"Oura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeko","family":"Koyamatsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Iimori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaori","family":"Fujita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2981-4035","authenticated-orcid":false,"given":"Takahiro","family":"Nemoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9859-6217","authenticated-orcid":false,"given":"Masahito","family":"Ikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0520-3654","authenticated-orcid":false,"given":"Noriyuki","family":"Tsumaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"69507_CR1","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1002\/dvdy.24479","volume":"246","author":"DM Ornitz","year":"2017","unstructured":"Ornitz, D. 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