{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T11:18:18Z","timestamp":1781090298599,"version":"3.54.1"},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,4,25]],"date-time":"2014-04-25T00:00:00Z","timestamp":1398384000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["R01-DK62515"],"award-info":[{"award-number":["R01-DK62515"]}]},{"name":"NIH","award":["P30-AR-46032"],"award-info":[{"award-number":["P30-AR-46032"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Anatomy"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The modeling of long bone surfaces during linear growth is a key developmental process, but its regulation is poorly understood. We report here that parathyroid hormone\u2010related peptide (<jats:styled-content style=\"fixed-case\">PTH<\/jats:styled-content>r<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>) expressed in the fibrous layer of the periosteum (<jats:styled-content style=\"fixed-case\">PO<\/jats:styled-content>) drives the osteoclastic (<jats:styled-content style=\"fixed-case\">OC<\/jats:styled-content>) resorption that models the metaphyseal\u2013diaphyseal junction (<jats:styled-content style=\"fixed-case\">MDJ<\/jats:styled-content>) in the proximal tibia and fibula during linear growth. <jats:styled-content style=\"fixed-case\">PTH<\/jats:styled-content>r<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content> was conditionally deleted (c<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content>) in the <jats:styled-content style=\"fixed-case\">PO<\/jats:styled-content> via <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>cleraxis gene targeting (<jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>cx\u2010<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>re). In the lateral tibia, c<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> of <jats:styled-content style=\"fixed-case\">PTH<\/jats:styled-content>r<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content> led to a failure of modeling, such that the normal concave <jats:styled-content style=\"fixed-case\">MDJ<\/jats:styled-content> was replaced by a mound\u2010like deformity. This was accompanied by a failure to induce receptor activator of NF\u2010kB ligand (<jats:styled-content style=\"fixed-case\">RANKL<\/jats:styled-content>) and a 75% reduction in <jats:styled-content style=\"fixed-case\">OC<\/jats:styled-content> number (<jats:italic>P\u2005<\/jats:italic>\u2264\u20050.001) on the cortical surface. The <jats:styled-content style=\"fixed-case\">MDJ<\/jats:styled-content> also displayed a curious threefold increase in endocortical osteoblast mineral apposition rate (<jats:italic>P\u2005<\/jats:italic>\u2264\u20050.001) and a thickened cortex, suggesting some form of coupling of endocortical bone formation to events on the <jats:styled-content style=\"fixed-case\">PO<\/jats:styled-content> surface. Because it fuses distally, the fibula is modeled only proximally and does so at an extraordinary rate, with an anteromedial cortex in <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\u20101 mice that was so moth\u2010eaten that a clear <jats:styled-content style=\"fixed-case\">PO<\/jats:styled-content> surface could not be identified. The c<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> fibula displayed a remarkable phenotype, with a misshapen club\u2010like metaphysis and an enlargement in the 3<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content> size of the entire bone, manifest as a 40\u201345% increase in the <jats:styled-content style=\"fixed-case\">PO<\/jats:styled-content> circumference at the <jats:styled-content style=\"fixed-case\">MDJ<\/jats:styled-content> (<jats:italic>P\u2005<\/jats:italic>\u2264\u20050.001) as well as the mid\u2010diaphysis (<jats:italic>P\u2005<\/jats:italic>\u2264\u20050.001). These tibial and fibular phenotypes were reproduced in a <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>cx\u2010<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>re\u2010driven <jats:styled-content style=\"fixed-case\">RANKL<\/jats:styled-content> c<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> mouse. We conclude that <jats:styled-content style=\"fixed-case\">PTH<\/jats:styled-content>r<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content> in the fibrous <jats:styled-content style=\"fixed-case\">PO<\/jats:styled-content> mediates the modeling of the <jats:styled-content style=\"fixed-case\">MDJ<\/jats:styled-content> of long bones during linear growth, and that in a highly susceptible system such as the fibula this surface modeling defines the size and shape of the entire bone.<\/jats:p>","DOI":"10.1111\/joa.12184","type":"journal-article","created":{"date-parts":[[2014,4,25]],"date-time":"2014-04-25T10:52:49Z","timestamp":1398423169000},"page":"71-82","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Periosteal <scp>PTH<\/scp>r<scp>P<\/scp> regulates cortical bone modeling during linear growth in mice"],"prefix":"10.1111","volume":"225","author":[{"given":"Meina","family":"Wang","sequence":"first","affiliation":[{"name":"Endocrine Section Department of Internal Medicine Yale University New Haven CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua N.","family":"VanHouten","sequence":"additional","affiliation":[{"name":"Endocrine Section Department of Internal Medicine Yale University New Haven CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali R.","family":"Nasiri","sequence":"additional","affiliation":[{"name":"Endocrine Section Department of Internal Medicine Yale University New Haven CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M.","family":"Tommasini","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Rehabilitation Yale University New Haven CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur E.","family":"Broadus","sequence":"additional","affiliation":[{"name":"Endocrine Section Department of Internal Medicine Yale University New Haven CT 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