{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T13:52:52Z","timestamp":1791035572703,"version":"4.1.0"},"reference-count":19,"publisher":"Walter de Gruyter GmbH","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Longitudinal bone growth in children depends on endochondral ossification within the epiphyseal growth plate, a process long viewed as a passive readout of systemic hormones but now recognized as an actively regulated, self-limiting process. This mini-review synthesizes recent evidence on chondrocyte biology, growth plate senescence, and the growth hormone (GH)\u2013insulin-like growth factor 1 (IGF-1) axis. Local paracrine networks establish precise antagonistic and synergistic interactions: fibroblast growth factor receptor 3 (FGFR3) suppresses chondrocyte proliferation via MAPK\/STAT signaling, while the C-type natriuretic peptide\/NPR2 pathway counters this via cGMP-mediated stimulation; the Indian hedgehog\u2013parathyroid hormone\u2013related protein feedback loop, the\n                    <jats:italic>SHOX<\/jats:italic>\n                    gene, and mechanical loading provide additional structural control. Growth plate senescence follows a proposed localized, cell-counting mechanism reflecting cumulative chondrocyte division that current evidence supports but that has not been established as the sole explanation for chronological variation in physeal closure. Estrogen is a key accelerant of this senescent process during puberty. Pathogenic variants in these local regulators underlie conditions such as achondroplasia and a minority of cases classified as idiopathic short stature, and mechanism-targeted therapies\u00a0\u2013\u00a0including vosoritide, a C-type natriuretic peptide analog, together with the FGFR3-directed tyrosine kinase inhibitor infigratinib and the once-weekly CNP prodrug navepegritide\u00a0\u2013\u00a0illustrate, for achondroplasia specifically, how targeting a defined paracrine lesion can produce growth responses that systemic hormone stimulation alone does not achieve in that disorder. For a limited group of monogenic growth-plate disorders, resolving these molecular networks is beginning to complement uniform systemic intervention with precision, mechanism-based therapy, although this paradigm remains investigational for the great majority of children with short stature.\n                  <\/jats:p>","DOI":"10.1515\/jpem-2026-0485","type":"journal-article","created":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T12:55:32Z","timestamp":1791032132000},"source":"Crossref","is-referenced-by-count":0,"title":["Growth plate senescence, chondrocyte biology, and the growth hormone\u2013insulin-like growth factor 1 axis in childhood growth"],"prefix":"10.1515","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9585-9461","authenticated-orcid":false,"given":"Ashraf T.","family":"Soliman","sequence":"first","affiliation":[{"name":"Department of Pediatrics , Division of Endocrinology, Hamad Medical Corporation , Doha , Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fawzia","family":"Alyafei","sequence":"additional","affiliation":[{"name":"Department of Pediatrics , Division of Endocrinology, Hamad Medical Corporation , Doha , Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9614-6511","authenticated-orcid":false,"given":"Nada","family":"Alaaraj","sequence":"additional","affiliation":[{"name":"Department of Pediatrics , Division of Endocrinology, Hamad Medical Corporation , Doha , Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noor","family":"Hamed","sequence":"additional","affiliation":[{"name":"Department of Pediatrics , Division of Endocrinology, Hamad Medical Corporation , Doha , Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shayma","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Pediatrics , Division of Endocrinology, Hamad Medical Corporation , Doha , Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"2026100312552796166_j_jpem-2026-0485_ref_001","doi-asserted-by":"crossref","unstructured":"Lui, JC, Nilsson, O, Baron, J. 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