{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:07:32Z","timestamp":1791187652127,"version":"4.1.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[1999,2,1]],"date-time":"1999-02-01T00:00:00Z","timestamp":917827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1999,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Bone sialoprotein (BSP) and osteopontin (OPN) are two major noncollagenous matrix proteins in mineralized connective tissue that have discrete roles in bone matrix formation, mineralization, and remodeling. The osteotropic secosteroid, 1,25-dihydroxyvitamin D3, a potent regulator of bone remodeling required for normal bone development, has been shown to exert differential effects on OPN and BSP expression by bone cells in vitro. To investigate these effects in vivo, we induced vitamin D3 deficiency in a transgenic mouse line (rBSP2.7Luc) that has a 2.7 kb rat BSP promoter linked to a luciferase reporter gene in its genome. Pregnant rBSP2.7Luc mice were fed vitamin D3\u2013deficient food and demineralized water for 6 weeks. Their offspring were weaned at 3 weeks of age and then fed vitamin D\u2013deficient food for an additional week. The control group were fed normal rodent pellets and water during the entire experimental procedure. Bone tissues from 40, 4-week-old offspring in each group were analyzed for BSP, OPN and luciferase expression. Vitamin D3\u2013deficient mice displayed a rachitic phenotype that included reduced size and malformation of bones. Assays of the BSP promoter transgene in calvariae, mandibles, and tibiae of the rachitic mice showed increases in luciferase activity of 3.1-, 1.9-, and 4.6-fold, respectively, when compared with control littermates. Semiquantitative reverse transcriptase polymerase chain reaction assays of BSP mRNA revealed increases of 7-, 74-, and 66-fold, respectively, in the same rachitic bones, while OPN mRNA was reduced 12.5-fold in calvariae and 2-fold in tibiae and mandibles. In situ hybridization using mouse cRNA probes revealed that the increased BSP expression and decreased OPN expression in the vitamin D3\u2013deficient mice was primarily in osteoblastic cells on the surface of calvariae and endosteal spaces of alveolar bone, on newly formed epiphyseal bone, and in cementoblasts and in hypertrophic chondrocytes. These studies are the first to show that BSP and OPN are differentially regulated by vitamin D3 in vivo, reflecting the diverse roles of these protein in bone remodeling. Moreover, the increased expression of the BSP transgene in the rachitic mice demonstrates that vitamin D3 regulation of BSP expression is mediated, in part, by element(s) within the 2.7 kb promoter region.<\/jats:p>","DOI":"10.1359\/jbmr.1999.14.2.221","type":"journal-article","created":{"date-parts":[[2006,4,26]],"date-time":"2006-04-26T20:05:40Z","timestamp":1146081940000},"page":"221-229","source":"Crossref","is-referenced-by-count":31,"title":["Altered Expression of Bone Sialoproteins in Vitamin D\u2013Deficient rBSP2.7Luc Transgenic Mice"],"prefix":"10.1093","volume":"14","author":[{"given":"Jake (Jinkun)","family":"Dr. Chen","sequence":"first","affiliation":[{"name":"Department of Pediatric Dentistry, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hangqing","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Don M.","family":"Ranly","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaro","family":"Sodek","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara D.","family":"Boyan","sequence":"additional","affiliation":[{"name":"Industry-University Cooperative Research Center, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,12,2]]},"reference":[{"key":"2024020713383863400_bib1","first-page":"297","volume-title":"Chemistry and Biology of Mineralized Tissues. Elsevier Science Publishers B.V.","author":"Sodek"},{"key":"2024020713383863400_bib2","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1002\/jbmr.5650070816","article-title":"Development expression of bone sialoprotein mRNA in rat mineralized connective tissues","volume":"7","author":"Chen","year":"1992","journal-title":"J Bone Miner Res"},{"key":"2024020713383863400_bib3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/03008209509016974","article-title":"Role of two mineral-associated adhesion molecules, osteopontin and bone sialoprotein, during cementogenesis","volume":"33","author":"MacNeil","year":"1995","journal-title":"Connect Tissue Res"},{"key":"2024020713383863400_bib4","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1002\/jcp.1041520305","article-title":"Temporal studies on the tissue compartmentalization of bone sialoprotein (BSP), osteopontin (OPN), and SPARC protein during bone formation in vitro","volume":"152","author":"Kasugai","year":"1992","journal-title":"J Cell Physiol"},{"key":"2024020713383863400_bib5","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1002\/jbmr.5650090212","article-title":"Temporal changes in matrix protein synthesis and mRNA expression during mineralized tissue formation by adult rat bone marrow cells in culture","volume":"9","author":"Yao","year":"1994","journal-title":"J Bone Miner Res"},{"key":"2024020713383863400_bib6","doi-asserted-by":"crossref","first-page":"8562","DOI":"10.1073\/pnas.90.18.8562","article-title":"Nucleation of hydroxyapatite by bone sialoprotein","volume":"90","author":"Hunter","year":"1993","journal-title":"Proc Natl Acad Sci USA"},{"key":"2024020713383863400_bib7","author":"Ganss"},{"key":"2024020713383863400_bib8","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/S0934-8832(11)80070-3","article-title":"Developmental expression of osteopontin (OPN) mRNA in rat tissues: Evidence for a role for OPN in bone formation and resorption","volume":"13","author":"Chen","year":"1993","journal-title":"Matrix"},{"key":"2024020713383863400_bib9","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1002\/jcb.240520212","article-title":"Induction of bone-related proteins, osteocalcin and osteopontin, and their matrix ultrastructural localization with development of chondrocyte hypertrophy in vitro","volume":"52","author":"Lian","year":"1993","journal-title":"J Cell Biochem"},{"key":"2024020713383863400_bib10","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1002\/(SICI)1097-0185(199606)245:2<394::AID-AR19>3.0.CO;2-K","article-title":"Secretion of osteopontin by macrophages and its accumulation at tissue surfaces during wound healing in mineralized tissues: A potential requirement for macrophage adhesion and phagocytosis","volume":"245","author":"McKee","year":"1996","journal-title":"Anat Record"},{"key":"2024020713383863400_bib11","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1111\/j.1749-6632.1995.tb44633.x","article-title":"Regulation of osteopontin expression in osteoblasts","volume":"760","author":"Sodek","year":"1995","journal-title":"Ann NY Acad Sci"},{"key":"2024020713383863400_bib12","doi-asserted-by":"crossref","first-page":"4473","DOI":"10.1073\/pnas.87.12.4473","article-title":"Osteopontin\u2014A possible anchor of osteoclasts to bone","volume":"87","author":"Reinholt","year":"1990","journal-title":"Proc Natl Acad Sci USA"},{"key":"2024020713383863400_bib13","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1242\/jcs.104.4.1013","article-title":"Expression of osteopontin mRNA by osteoclasts and osteoblasts in modelling adult human bone","volume":"104","author":"Merry","year":"1993","journal-title":"J Cell Sci"},{"key":"2024020713383863400_bib14","doi-asserted-by":"crossref","first-page":"9901","DOI":"10.1016\/S0021-9258(18)98430-9","article-title":"Interactions between the bone matrix proteins osteopontin and bone sialoprotein and the osteoclast integrin alpha v beta 3 potentiate bone resorption","volume":"268","author":"Ross","year":"1993","journal-title":"J Biol Chem"},{"key":"2024020713383863400_bib15","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1002\/jcp.1041470115","article-title":"Expression of bone matrix proteins associated with mineralized tissue formation by adult rat bone marrow cells in vitro: Inductive effects of dexamethasone on the osteoblastic phenotype","volume":"147","author":"Kasugai","year":"1991","journal-title":"J Cell Physiol"},{"key":"2024020713383863400_bib16","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1042\/bj3180219","article-title":"Identification of a vitamin D3-response element that overlaps a unique inverted TATA box in the rat bone sialoprotein gene","volume":"318","author":"Kim","year":"1996","journal-title":"Biochem J"},{"key":"2024020713383863400_bib17","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1002\/(SICI)1097-4652(199610)169:1<115::AID-JCP12>3.0.CO;2-C","article-title":"Effects of osteogenic protein-1 (OP-1, BMP-7) on bone matrix protein expression by fetal rat calvarial cells are differentiation stage specific","volume":"169","author":"Li","year":"1996","journal-title":"J Cell Physiol"},{"key":"2024020713383863400_bib18","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/S0174-173X(87)80036-5","article-title":"1,25-dihydroxyvitamin D3 regulates the biosynthesis of osteopontin, a bone-derived cell attachment protein, in clonal osteoblast-like osteosarcoma cells","volume":"7","author":"Prince","year":"1987","journal-title":"Coll Relat Res"},{"key":"2024020713383863400_bib19","doi-asserted-by":"crossref","first-page":"3183","DOI":"10.1083\/jcb.109.6.3183","article-title":"Regulation of bone sialoprotein mRNA by steroid hormones","volume":"109","author":"Oldberg","year":"1989","journal-title":"J Cell Biol"},{"key":"2024020713383863400_bib20","doi-asserted-by":"crossref","first-page":"41","DOI":"10.3109\/03008209609028892","article-title":"Regulation of bone sialoprotein and osteopontin mRNA expression by dexamethasone and 1,25-dihydroxyvitamin D3 in rat bone organ cultures","volume":"34","author":"Chen","year":"1996","journal-title":"Connect Tissue Res"},{"key":"2024020713383863400_bib21","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1111\/j.1749-6632.1995.tb44625.x","article-title":"Osteopontin-induced modifications of cellular functions","volume":"760","author":"Denhardt","year":"1995","journal-title":"Ann NY Acad Sci"},{"key":"2024020713383863400_bib22","first-page":"631","article-title":"Rickets induced by calcium or phosphate depletion","volume":"71","author":"Abugassa","year":"1990","journal-title":"Int J Exp Path"},{"key":"2024020713383863400_bib23","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1002\/jbmr.5650110513","article-title":"Expression of rat bone sialoprotein promoter in transgenic mice","volume":"11","author":"Chen","year":"1996","journal-title":"J Bone Miner Res"},{"key":"2024020713383863400_bib24","doi-asserted-by":"crossref","first-page":"33","DOI":"10.3109\/03008209609029172","article-title":"Dexamethasone stimulates luciferase gene expression through the rat bone sialoprotein gene promoter in transgenic mice","volume":"35","author":"Chen","year":"1996","journal-title":"Connect Tissue Res"},{"key":"2024020713383863400_bib25","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1007\/BF00292337","article-title":"Murine bone sialoprotein (BSP): cDNA cloning, mRNA expression, and genetic mapping","volume":"5","author":"Young","year":"1994","journal-title":"Mamm Genome"},{"key":"2024020713383863400_bib26","doi-asserted-by":"crossref","first-page":"9682","DOI":"10.1016\/S0021-9258(18)60584-8","article-title":"Osteopontin, a transformation-associated cell adhesion phosphoprotein, is induced by 12-O-tetradecanoylphorbol 13-acetate in mouse epidermis","volume":"264","author":"Craig","year":"1989","journal-title":"J Biol Chem"},{"key":"2024020713383863400_bib27","doi-asserted-by":"crossref","first-page":"9717","DOI":"10.1073\/pnas.86.24.9717","article-title":"Quantitation of mRNA by the polymerase chain reaction","volume":"86","author":"Wang","year":"1989","journal-title":"Proc Natl Acad Sci USA"},{"key":"2024020713383863400_bib28","first-page":"1272","volume-title":"Pathology","author":"Schiller"},{"key":"2024020713383863400_bib29","first-page":"329","volume-title":"Vitamin D","author":"Suda"},{"key":"2024020713383863400_bib30","first-page":"305","volume-title":"Vitamin D","author":"Tanaka"},{"key":"2024020713383863400_bib31","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1042\/bj3100033","article-title":"An inverted TATA box directs downstream transcription of the bone sialoprotein gene","volume":"310","author":"Li","year":"1995","journal-title":"Biochem J"},{"key":"2024020713383863400_bib32","first-page":"183","article-title":"Glucocorticoid regulation of bone sialoprotein (BSP) gene expression: Identification of a glucocorticoid response element in the bone sialoprotein gene promoter","volume":"230","author":"Ogata","year":"1995","journal-title":"Eur J Biochem"},{"key":"2024020713383863400_bib33","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/S0945-053X(96)90153-5","article-title":"AP-1 regulation of the rat bone sialoprotein gene transcription is mediated through a TPA response element within a glucocorticoid response unit in the gene promoter","volume":"15","author":"Yamauchi","year":"1996","journal-title":"Matrix Biol"},{"key":"2024020713383863400_bib34","doi-asserted-by":"crossref","first-page":"9995","DOI":"10.1073\/pnas.87.24.9995","article-title":"Identification of a DNA sequence responsible for binding of the 1,25-dihydroxyvitamin D3 receptor and 1,25-dihydroxyvitamin D3 enhancement of mouse secreted phosphoprotein 1 (SPP-1 or osteopontin) gene expression","volume":"87","author":"Noda","year":"1990","journal-title":"Proc Natl Acad Sci USA"},{"key":"2024020713383863400_bib35","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1111\/j.1432-1033.1992.tb17092.x","article-title":"Characterization of the promoter region of the porcine opn (osteopontin, secreted phosphoprotein 1) gene: Identification of positive and negative regulatory elements and a \u2018silent\u2019 second promoter","volume":"207","author":"Zhang","year":"1992","journal-title":"Eur J Biochem"},{"key":"2024020713383863400_bib36","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/BF02388394","article-title":"Bone sialoprotein mRNA expression and ultrastructural localization in fetal porcine calvarial bone: Comparisons with osteopontin","volume":"26","author":"Chen","year":"1994","journal-title":"Histochem J"},{"key":"2024020713383863400_bib37","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1210\/endo.134.5.8156925","article-title":"1,25-dihydroxyvitamin D3 stimulates adipocyte differentiation in cultures of fetal rat calvaria cells: Comparison with the effects of dexamethasone","volume":"134","author":"Bellows","year":"1994","journal-title":"Endocrinology"},{"key":"2024020713383863400_bib38","doi-asserted-by":"crossref","first-page":"7583","DOI":"10.1016\/S0021-9258(19)39154-9","article-title":"Characterization of fetal porcine bone sialoproteins, secreted phosphoprotein I (SPPI, osteopontin), bone sialoprotein, and a 23-kDa glycoprotein: Demonstration that the 23-kDa glycoprotein is derived from the carboxyl terminus of SPPI","volume":"265","author":"Zhang","year":"1990","journal-title":"J Biol Chem"},{"key":"2024020713383863400_bib39","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/j.1749-6632.1995.tb44620.x","article-title":"Characterization of the rat osteopontin gene: Evidence for two vitamin D response elements","volume":"760","author":"Ridall","year":"1995","journal-title":"Ann NY Acad Sci"},{"key":"2024020713383863400_bib40","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1083\/jcb.99.2.471","article-title":"Identification and characterization of osteoclast-like cells and their progenitors in cultures of feline marrow mononuclear cells","volume":"99","author":"Ibbotson","year":"1984","journal-title":"J Cell Biol"},{"key":"2024020713383863400_bib41","doi-asserted-by":"crossref","first-page":"8213","DOI":"10.1073\/pnas.82.23.8213","article-title":"1,25-dihydroxyvitamin D3 causes formation of multinucleated cells with several osteoclast characteristics in cultures of primate marrow","volume":"82","author":"Roodman","year":"1985","journal-title":"Proc Natl Acad Sci USA"},{"key":"2024020713383863400_bib42","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1007\/BF02409454","article-title":"Role of osteoblasts in hormonal control of bone resorption\u2014A hypothesis","volume":"33","author":"Rodan","year":"1981","journal-title":"Calcif Tissue Int"},{"key":"2024020713383863400_bib43","doi-asserted-by":"crossref","first-page":"9938","DOI":"10.1016\/S0021-9258(19)81608-3","article-title":"Type X collagen alterations in rachitic chick epiphyseal growth cartilage","volume":"263","author":"Reginato","year":"1988","journal-title":"J Biol Chem"}],"container-title":["Journal of Bone and Mineral Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1359%2Fjbmr.1999.14.2.221","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/14\/2\/221\/56601340\/5650140209.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/14\/2\/221\/56601340\/5650140209.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T14:57:46Z","timestamp":1710341866000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/14\/2\/221-229\/7514867"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,2,1]]},"references-count":43,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2009,12,2]]},"published-print":{"date-parts":[[1999,2,1]]}},"URL":"https:\/\/doi.org\/10.1359\/jbmr.1999.14.2.221","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[1999,2,1]]},"published":{"date-parts":[[1999,2,1]]}}}