{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T14:38:43Z","timestamp":1792593523739,"version":"4.5.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>The growth plate is a spatially organized cartilage structure that drives longitudinal bone growth and is particularly vulnerable to nutritional imbalance, systemic disease, trauma, and drug exposure during childhood. Retinoic acid (RA), the bioactive metabolite of vitamin A, regulates transcription through retinoic acid receptors (RAR\u03b1, RAR\u03b2, and RAR\u03b3). Its skeletal effects depend on concentration, developmental timing, tissue context, and receptor subtype. Physiologic RA homeostasis contributes to orderly chondrocyte maturation, whereas excessive or spatially inappropriate signaling can suppress proliferation, alter hypertrophic differentiation and extracellular matrix, and promote premature growth plate senescence or closure in experimental models. This narrative review integrates evidence on RA metabolism, RAR-dependent chondrocyte fate, and experimental RAR antagonists. Model-dependent antagonist effects include concurrent prevention of hedgehog inhibitor-associated closure and early post-injury attenuation of growth inhibition in juvenile mice; prevention during induction is not reversal of established physeal damage. Human zone-specific receptor biology remains insufficiently resolved, and apparently conflicting findings reflect differences in receptor pharmacology, tissue, developmental stage, timing, dose, and endpoint. Pediatric experience with systemic retinoids, including isotretinoin and the RAR\u03b3 agonist palovarotene, underscores the developmental hazards of pathway modulation. Future studies should prioritize validated human growth plate models, receptor-subtype pharmacology, and longitudinal skeletal monitoring. RAR antagonism remains a preclinical, hypothesis-generating strategy requiring rigorous dose-window and long-term safety evaluation before pediatric clinical investigation.<\/jats:p>","DOI":"10.3389\/fendo.2026.1962290","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:01:05Z","timestamp":1791288065000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Retinoic acid signaling in growth plate development: receptor-specific effects, antagonist evidence, and pediatric translational considerations"],"prefix":"10.3389","volume":"17","author":[{"given":"Yutong","family":"Xing","sequence":"first","affiliation":[{"name":"Department of Paediatrics, The Second Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiying","family":"Fan","sequence":"additional","affiliation":[{"name":"Hebei University of Chinese Medicine","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaixi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, The Second Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, The Second Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Xuan","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, The Second Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huifeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, The Second Hospital of Hebei 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