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Previously, STC1 expression was found to be increased by 1,25-dihydroxyvitamin D\n                    <jats:sub>3<\/jats:sub>\n                    [1,25(OH)\n                    <jats:sub>2<\/jats:sub>\n                    D\n                    <jats:sub>3<\/jats:sub>\n                    ] administration in renal proximal tubular cells. In this study, we investigated whether STC1 directly regulates osteoblast differentiation or reciprocally controls the effects of 1,25(OH)\n                    <jats:sub>2<\/jats:sub>\n                    D\n                    <jats:sub>3<\/jats:sub>\n                    on osteoblasts to contribute to bone homeostasis. We found that STC1 inhibited osteoblast differentiation in vitro and bone morphogenetic protein 2 (BMP2)-induced ectopic bone formation in vivo. Moreover, 1,25(OH)\n                    <jats:sub>2<\/jats:sub>\n                    D\n                    <jats:sub>3<\/jats:sub>\n                    increased STC1 expression through direct binding to the\n                    <jats:italic>Stc1<\/jats:italic>\n                    promoter of the vitamin D receptor (VDR). STC1 activated the 1,25(OH)\n                    <jats:sub>2<\/jats:sub>\n                    D\n                    <jats:sub>3<\/jats:sub>\n                    \u2013VDR signaling pathway through the upregulation of VDR expression mediated by the inhibition of Akt phosphorylation in osteoblasts. STC1 further increased the effects of 1,25(OH)\n                    <jats:sub>2<\/jats:sub>\n                    D\n                    <jats:sub>3<\/jats:sub>\n                    on receptor activator of nuclear factor-\u03baB ligand (RANKL) secretion and inhibited osteoblast differentiation by exhibiting a positive correlation with 1,25(OH)\n                    <jats:sub>2<\/jats:sub>\n                    D\n                    <jats:sub>3<\/jats:sub>\n                    . The long-bone phenotype of transgenic mice overexpressing STC1 specifically in osteoblasts was not significantly different from that of wild-type mice. However, compared with that in the wild-type mice, 1,25(OH)\n                    <jats:sub>2<\/jats:sub>\n                    D\n                    <jats:sub>3<\/jats:sub>\n                    administration significantly decreased bone mass in the STC1 transgenic mice. Collectively, these results suggest that STC1 negatively regulates osteoblast differentiation and bone formation; however, the inhibitory effect of STC1 on osteoblasts is transient and can be reversed under normal conditions. Nevertheless, the synergistic effect of STC1 and 1,25(OH)\n                    <jats:sub>2<\/jats:sub>\n                    D\n                    <jats:sub>3<\/jats:sub>\n                    through 1,25(OH)\n                    <jats:sub>2<\/jats:sub>\n                    D\n                    <jats:sub>3<\/jats:sub>\n                    administration may reduce bone mass by inhibiting osteoblast differentiation.\n                  <\/jats:p>","DOI":"10.1038\/s12276-024-01302-2","type":"journal-article","created":{"date-parts":[[2024,9,1]],"date-time":"2024-09-01T21:02:04Z","timestamp":1725224524000},"page":"1991-2001","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Stanniocalcin 1 and 1,25-dihydroxyvitamin D3 cooperatively regulate bone mineralization by osteoblasts"],"prefix":"10.1038","volume":"56","author":[{"given":"Jung Ha","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kabsun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inyoung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Semun","family":"Seong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6279-6487","authenticated-orcid":false,"given":"Jeong-Tae","family":"Koh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nacksung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,9,2]]},"reference":[{"key":"1302_CR1","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1016\/0016-6480(86)90149-8","volume":"63","author":"GF Wagner","year":"1986","unstructured":"Wagner, G. 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