{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T02:53:40Z","timestamp":1789786420596,"version":"4.0.1"},"reference-count":21,"publisher":"The Endocrine Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,10,1]]},"abstract":"<jats:p>Rickets is a growth plate abnormality observed in growing animals and humans. Rachitic expansion of the hypertrophic chondrocyte layer of the growth plate, in the setting of hypophosphatemia, is due to impaired apoptosis of these cells. Rickets is observed in humans and mice with X-linked hypophosphatemia that is associated with renal phosphate wasting secondary to elevated levels of fibroblast growth factor-23. Rickets is also seen in settings of impaired vitamin D action, due to elevated PTH levels that increase renal phosphate excretion. However, mice with hypophosphatemia secondary to ablation of the renal sodium-dependent phosphate transport protein 2a (Npt2a), have not been reported to develop rickets. Because activation of the mitochondrial apoptotic pathway by phosphate is required for hypertrophic chondrocyte apoptosis in vivo, investigations were undertaken to address this paradox. Analyses of the Npt2a null growth plate demonstrate expansion of the hypertrophic chondrocyte layer at 2 wk of age, with resolution of this abnormality by 5 wk of age. This is temporally associated with an increase in circulating levels of 1,25-dihydroxyvitamin D. To address whether the receptor-dependent actions of this steroid hormone are required for normalization of the growth plate phenotype, the Npt2a null mice were mated with mice lacking the vitamin D receptor or were rendered vitamin D deficient. These studies demonstrate that the receptor-dependent actions of 1,25-dihydroxyvitamin D are required for maintenance of a normal growth plate phenotype in the Npt2a null mice.<\/jats:p>","DOI":"10.1210\/en.2010-0354","type":"journal-article","created":{"date-parts":[[2010,8,5]],"date-time":"2010-08-05T03:01:11Z","timestamp":1280977271000},"page":"4607-4612","source":"Crossref","is-referenced-by-count":39,"title":["The Receptor-Dependent Actions of 1,25-Dihydroxyvitamin D Are Required for Normal Growth Plate Maturation in NPt2a Knockout Mice"],"prefix":"10.1210","volume":"151","author":[{"given":"Susanne U.","family":"Miedlich","sequence":"first","affiliation":[{"name":"Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric D.","family":"Zhu","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Sabbagh","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie B.","family":"Demay","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2010,8,4]]},"reference":[{"key":"2020071613444931400_R1","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.jsbmb.2004.03.026","article-title":"Rescue of the phenotype of CYP27B1 (1alpha-hydroxylase)-deficient mice.","volume":"89\u201390","author":"Dardenne","year":"2004","journal-title":"J Steroid Biochem Mol 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