Jung Ha Kim, Kabsun Kim, Inyoung Kim, Semun Seong, Jeong-Tae Koh, Nacksung Kim
{"title":"Stanniocalcin 1 和 1,25-二羟维生素 D3 可协同调节成骨细胞的骨矿化。","authors":"Jung Ha Kim, Kabsun Kim, Inyoung Kim, Semun Seong, Jeong-Tae Koh, Nacksung Kim","doi":"10.1038/s12276-024-01302-2","DOIUrl":null,"url":null,"abstract":"Stanniocalcin 1 (STC1) is a calcium- and phosphate-regulating hormone that is expressed in all tissues, including bone tissues, and is involved in calcium and phosphate homeostasis. Previously, STC1 expression was found to be increased by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] 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)2D3 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)2D3 increased STC1 expression through direct binding to the Stc1 promoter of the vitamin D receptor (VDR). STC1 activated the 1,25(OH)2D3–VDR 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)2D3 on receptor activator of nuclear factor-κB ligand (RANKL) secretion and inhibited osteoblast differentiation by exhibiting a positive correlation with 1,25(OH)2D3. 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)2D3 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)2D3 through 1,25(OH)2D3 administration may reduce bone mass by inhibiting osteoblast differentiation. In the field of bone health, it’s important to understand how our bodies control bone creation. This research investigates how Stanniocalcin 1 and 1,25-dihydroxyvitamin D3 work together to affect bone mineralization by osteoblasts. The team used mouse models and cell cultures in their experiment. They found that STC1 alone can slow down osteoblast differentiation and bone creation, but this effect is stronger when 1,25-dihydroxyvitamin D3 is also present. This suggests a complex relationship that could affect bone health. They conclude that the combined regulation by STC1 and 1,25-dihydroxyvitamin D3 is a key factor in bone mineralization, providing new insights into managing bone health. This knowledge could lead to treatments for bone diseases by targeting these pathways. Future research may show how to adjust these interactions for treatment benefits, potentially improving results for those with bone health problems. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":9.5000,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01302-2.pdf","citationCount":"0","resultStr":"{\"title\":\"Stanniocalcin 1 and 1,25-dihydroxyvitamin D3 cooperatively regulate bone mineralization by osteoblasts\",\"authors\":\"Jung Ha Kim, Kabsun Kim, Inyoung Kim, Semun Seong, Jeong-Tae Koh, Nacksung Kim\",\"doi\":\"10.1038/s12276-024-01302-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Stanniocalcin 1 (STC1) is a calcium- and phosphate-regulating hormone that is expressed in all tissues, including bone tissues, and is involved in calcium and phosphate homeostasis. Previously, STC1 expression was found to be increased by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] 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)2D3 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)2D3 increased STC1 expression through direct binding to the Stc1 promoter of the vitamin D receptor (VDR). STC1 activated the 1,25(OH)2D3–VDR 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)2D3 on receptor activator of nuclear factor-κB ligand (RANKL) secretion and inhibited osteoblast differentiation by exhibiting a positive correlation with 1,25(OH)2D3. 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)2D3 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)2D3 through 1,25(OH)2D3 administration may reduce bone mass by inhibiting osteoblast differentiation. In the field of bone health, it’s important to understand how our bodies control bone creation. This research investigates how Stanniocalcin 1 and 1,25-dihydroxyvitamin D3 work together to affect bone mineralization by osteoblasts. The team used mouse models and cell cultures in their experiment. They found that STC1 alone can slow down osteoblast differentiation and bone creation, but this effect is stronger when 1,25-dihydroxyvitamin D3 is also present. This suggests a complex relationship that could affect bone health. They conclude that the combined regulation by STC1 and 1,25-dihydroxyvitamin D3 is a key factor in bone mineralization, providing new insights into managing bone health. This knowledge could lead to treatments for bone diseases by targeting these pathways. Future research may show how to adjust these interactions for treatment benefits, potentially improving results for those with bone health problems. 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Stanniocalcin 1 and 1,25-dihydroxyvitamin D3 cooperatively regulate bone mineralization by osteoblasts
Stanniocalcin 1 (STC1) is a calcium- and phosphate-regulating hormone that is expressed in all tissues, including bone tissues, and is involved in calcium and phosphate homeostasis. Previously, STC1 expression was found to be increased by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] 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)2D3 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)2D3 increased STC1 expression through direct binding to the Stc1 promoter of the vitamin D receptor (VDR). STC1 activated the 1,25(OH)2D3–VDR 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)2D3 on receptor activator of nuclear factor-κB ligand (RANKL) secretion and inhibited osteoblast differentiation by exhibiting a positive correlation with 1,25(OH)2D3. 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)2D3 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)2D3 through 1,25(OH)2D3 administration may reduce bone mass by inhibiting osteoblast differentiation. In the field of bone health, it’s important to understand how our bodies control bone creation. This research investigates how Stanniocalcin 1 and 1,25-dihydroxyvitamin D3 work together to affect bone mineralization by osteoblasts. The team used mouse models and cell cultures in their experiment. They found that STC1 alone can slow down osteoblast differentiation and bone creation, but this effect is stronger when 1,25-dihydroxyvitamin D3 is also present. This suggests a complex relationship that could affect bone health. They conclude that the combined regulation by STC1 and 1,25-dihydroxyvitamin D3 is a key factor in bone mineralization, providing new insights into managing bone health. This knowledge could lead to treatments for bone diseases by targeting these pathways. Future research may show how to adjust these interactions for treatment benefits, potentially improving results for those with bone health problems. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
期刊介绍:
Experimental & Molecular Medicine (EMM) stands as Korea's pioneering biochemistry journal, established in 1964 and rejuvenated in 1996 as an Open Access, fully peer-reviewed international journal. Dedicated to advancing translational research and showcasing recent breakthroughs in the biomedical realm, EMM invites submissions encompassing genetic, molecular, and cellular studies of human physiology and diseases. Emphasizing the correlation between experimental and translational research and enhanced clinical benefits, the journal actively encourages contributions employing specific molecular tools. Welcoming studies that bridge basic discoveries with clinical relevance, alongside articles demonstrating clear in vivo significance and novelty, Experimental & Molecular Medicine proudly serves as an open-access, online-only repository of cutting-edge medical research.