Stanniocalcin 1 and 1,25-dihydroxyvitamin D3 cooperatively regulate bone mineralization by osteoblasts
2
조회
0
다운로드
0
인용
0
참고문헌
초록
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.
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.
참고문헌 (39)
- Wagner, G. F., "Purification, characteriza tion, and bioassay of teleocalcin, a glycoprotein from salmon corpuscles of Stannius", Gen Comp Endocrinol, 63, pp.481~491 (1986)
- Lafeber, F. P., "Hypocalcin from Stannius corpuscles inhibits gill calcium uptake in trout", Am J Physiol, 254, pp.R891~R896 (1988)
- Wagner, G. F., "Molecular cloning and cDNA sequence analysis of coho salmon stanniocalcin", Mol Cell Endocrinol, 90, pp.7~15 (1992)
- Chang, A. C., "A novel human cDNA highly homologous to the fish hormone stanniocalcin", Mol Cell Endocrinol, 112, pp.241~247 (1995)
- Varghese, R., "Comparative analysis of mammalian stanniocalcin genes", Endocrinology, 139, pp.4714~4725 (1998)
- Yoshiko, Y., "Stanniocalcin 1 stimulates osteoblast dif ferentiation in rat calvaria cell cultures", Endocrinology, 144, pp.4134~4143 (2003)
- Olsen, H. S., "Human stanniocalcin : a possible hormonal regulator of mineral metabolism", Proc Natl Acad Sci USA, 93, pp.1792~1796 (1996)
- Chang, A. C., "Identification of a second stanniocalcin cDNA in mouse and human : stanniocalcin 2", Mol Cell Endocrinol, 141, pp.95~99 (1998)
- De Niu, P., "Development of a human stanniocalcin radioimmunoassay : serum and tissue hormone levels and pharmacokinetics in the rat", Mol Cell Endocrinol, 162, pp.131~144 (2000)
- Yoshiko, Y., "Stanniocalcin 1 (STC1) protein and mRNA are developmentally regulated during embryonic mouse osteogenesis: the potential of stc1 as an autocrine", paracrine factor for osteoblast development and bone formation, 2002, pp.50, 483~492
- Haddad, M., "Immunocytochemical localization of stanniocalcin cells in the rat kidney", Endocrinology, 137, pp.2113~2117 (1996)
- De Niu, P., "Immunolocalization of stan niocalcin in human kidney", Mol Cell Endocrinol, 137, pp.155~159 (1998)
- Wong, C. K., "The co-localization of stanniocalcin protein, mRNA and kidney cell markers in the rat kidney", J Endocrinol, 158, pp.183~189 (1998)
- Yoshiko, Y., "In situ hybridization analysis of stanniocalcin mRNA expressing cells in the mouse kidney", Mol Cell Endocrinol, 141, pp.37~40 (1998)
- Yoshiko, Y., "Evidence for stanniocalcin gene expression in mammalian bone", Endocrinology, 140, pp.1869~1874 (1999)
- Chang, A. C., "The murine stanniocalcin 1 gene is not essential for growth and development", MolCellBiol, 25, pp.10604~10610 (2005)
- Filvaroff, E. H., "Stanniocalcin 1 alters muscle and bone structure and function in transgenic mice", Endocrinology, 143, pp.3681~3690 (2002)
- Jiang, W. Q., "The distribution of stanniocalcin 1 protein in fetal mouse tissues suggests a role in bone and muscle development", J Endocrinol, 165, pp.457~466 (2000)
- Stasko, S. E., "Possible roles for stanniocalcin during early skeletal patterning and joint formation in the mouse", J Endocrinol, 171, pp.237~248 (2001)
- Michigami, T., "Roles of Phosphate in Skeleton", Front Endocrinol, 10, pp.180~ (2019)
- Huitema, L. F., "Entpd5 is essential for skeletal mineralization and regulates phosphate homeostasis in zebrafish", Proc Natl Acad Sci USA, 109, pp.21372~21377 (2012)
- Sekaran, S., "The physiological and pathological role of tissue nonspecific alkaline phosphatase beyond mineralization", Biomolecules, 11, pp.1564~ (2021)
- Yadav, M. C., "Loss of skeletal mineralization by the simultaneous ablation of PHOSPHO1 and alkaline phosphatase function : a unified model of the mechan isms of initiation of skeletal calcification", J Bone Min Res, 26, pp.286~297 (2011)
- Stewart, A. J., "The presence of PHOSPHO1 in matrix vesicles and its devel opmental expression prior to skeletal mineralization", Bone, 39, pp.1000~1007 (2006)
- Murshed, M., "Unique coex pression in osteoblasts of broadly expressed genes accounts for the spatial restriction of ECM mineralization to bone", Genes Dev, 19, pp.1093~1104 (2005)
- Michigami, T., "Skeletal mineralization : mechanisms and diseases", Ann Pediatr Endocrinol Metab, 24, pp.213~219 (2019)
- Johnston, J., "Human stanniocalcin-1 or-2 expressed in mice reduces bone size and severely inhibits cranial intramembranous bone growth", Transgen Res, 19, pp.1017~1039 (2010)
- Han, A., "Position statement : vitamin d intake to prevent osteoporosis and fracture in adults", J Bone Metab, 29, pp.205~215 (2022)
- Kim, J. H., "Downregulation of Runx2 by 1, 25-Dihydroxyvitamin D3 induces the transdifferentiation of Osteoblasts to Adipocytes", Int J Mol Sci, 17, pp.770~ (2016)
- Hung, N. T., "Up-regulation of stanniocalcin 1 expression by 1, 25-dihydroxy vitamin D(3)and parathyroid hormone in renal proximal tubular cells", J Clin Biochem Nutr, 50, pp.227~233 (2012)
- Laird, E., "Vitamin D and bone health: potential mechanisms", Nutrients, 2, pp.693~724 (2010)
- van Driel, M., "Vitamin D endocrine system and osteoblasts", Bonekey Rep, 3, pp.493~ (2014)
- van de Peppel, J., "Vitamin D and gene networks in human osteoblasts", Front Physiol, 5, pp.137~ (2014)
- Anderson, H. C., "Molecular biology of matrix vesicles", Clin Orthop Relat Res, 314, pp.266~280 (1995)
- Gardiner, E. M., "Increased formation and decreased resorption of bone in mice with elevated vitamin D receptor in mature cells of the osteoblastic lineage", FASEB J, 14, pp.1908~1916 (2000)
- Yamamoto, Y., "Vitamin D receptor in osteoblasts is a negative regulator of bone mass control", Endocrinology, 154, pp.1008~1020 (2013)
- van Driel, M., "Evidence for auto", paracrine actions of vitamin D in bone : 1alpha-hydroxylase expression and activity in human bone cells, 2006, pp.20, 2417~2419
- LeBoff, M. S., "Supplemental Vitamin D and incident fractures in midlife and older adults", N. Engl J Med, 387, pp.299~309 (2022)
- Sanders, K. M., "Annual high-dose oral vitamin D and falls and fractures in older women : a randomized controlled trial", Jama, 303, pp.1815~1822 (2010)