{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T02:21:09Z","timestamp":1791426069111,"version":"4.3.3"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2003,6,1]],"date-time":"2003-06-01T00:00:00Z","timestamp":1054425600000},"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":[[2003,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Human osteoblast phenotypes that support osteoclast differentiation and bone formation are not well characterized. Osteoblast differentiation markers were examined in relation to RANKL expression. RANKL expression was induced preferentially in immature cells. These results support an important link between diverse osteoblast functions.<\/jats:p>\n               <jats:p>Cells of the osteoblast lineage support two apparently distinct functions: bone formation and promotion of osteoclast formation. The aim of this study was to examine the relationship between these phenotypes in human osteoblasts (NHBC), in terms of the pre-osteoblast marker, STRO-1, and the mature osteoblast marker, alkaline phosphatase (AP), and the expression of genes involved in osteoclast formation, RANKL and OPG. The osteotropic stimuli, 1\u03b1,25(OH)2vitamin D3 (vitD3) and dexamethasone, were found to have profound proliferative and phenotypic effects on NHBCs. VitD3 inhibited NHBC proliferation and increased the percentage of cells expressing STRO-1 over an extended culture period, implying that vitD3 promotes and maintains an immature osteogenic phenotype. Concomitantly, RANKL mRNA expression was upregulated and maintained in NHBC in response to vitD3. Dexamethasone progressively promoted the proliferation of AP-expressing cells, resulting in the overall maturation of the cultures. Dexamethasone had little effect on RANKL mRNA expression and downregulated OPG mRNA expression in a donor-dependent manner. Regression analysis showed that RANKL mRNA expression was associated negatively with the percentage of cells expressing AP (p &amp;lt; 0.01) in vitD3- and dexamethasone-treated NHBCs. In contrast, RANKL mRNA expression was associated positively with the percentage of STRO-1+ cells (p &amp;lt; 0.01). In NHBCs sorted by FACS based on STRO-1 expression (STRO-1bright and STRO-1dim populations), it was found that vitD3 upregulated the expression of RANKL mRNA preferentially in STRO-1bright cells. The results suggest that immature osteoblasts respond to osteotropic factors in a potentially pro-osteoclastogenic manner. Additionally, the dual roles of osteoblasts, in supporting osteoclastogenesis or forming bone, may be performed by the same lineage of cells at different stages of their maturation.<\/jats:p>","DOI":"10.1359\/jbmr.2003.18.6.1088","type":"journal-article","created":{"date-parts":[[2006,4,26]],"date-time":"2006-04-26T23:31:38Z","timestamp":1146094298000},"page":"1088-1098","source":"Crossref","is-referenced-by-count":216,"title":["RANKL Expression Is Related to the Differentiation State of Human Osteoblasts"],"prefix":"10.1093","volume":"18","author":[{"given":"Gerald J","family":"Atkins","sequence":"first","affiliation":[{"name":"Department of Orthopaedics and Trauma, University of Adelaide, Adelaide, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiota","family":"Kostakis","sequence":"additional","affiliation":[{"name":"Division of Haematology, Institute of Medical and Veterinary Science, Adelaide, South Australia, Australia"},{"name":"Department of Orthopaedics and Trauma, University of Adelaide, Adelaide, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beiqing","family":"Pan","sequence":"additional","affiliation":[{"name":"Division of Haematology, Institute of Medical and Veterinary Science, Adelaide, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Farrugia","sequence":"additional","affiliation":[{"name":"Division of Haematology, Institute of Medical and Veterinary Science, Adelaide, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stan","family":"Gronthos","sequence":"additional","affiliation":[{"name":"Division of Haematology, Institute of Medical and Veterinary Science, Adelaide, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Evdokiou","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Trauma, University of Adelaide, Adelaide, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Harrison","sequence":"additional","affiliation":[{"name":"Division of Haematology, Institute of Medical and Veterinary Science, Adelaide, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M","family":"Findlay","sequence":"additional","affiliation":[{"name":"These authors share senior author status on this manuscript"},{"name":"Department of Orthopaedics and Trauma, University of Adelaide, Adelaide, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew Cw","family":"Zannettino","sequence":"additional","affiliation":[{"name":"These authors share senior author status on this manuscript"},{"name":"Division of Haematology, Institute of Medical and Veterinary Science, Adelaide, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,12,2]]},"reference":[{"key":"2024013019135583400_bib1","doi-asserted-by":"crossref","first-page":"S37","DOI":"10.1007\/BF02406132","article-title":"The cellular basis of bone remodeling: The quantum concept reexamined in light of recent advances in the cell biology of bone","volume":"36","author":"Parfitt","year":"1984","journal-title":"Calcif Tissue Int"},{"key":"2024013019135583400_bib2","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1359\/jbmr.2002.17.1.77","article-title":"The bone lining cell: Its role in cleaning Howship's lacunae and initiating bone formation","volume":"17","author":"Everts","year":"2002","journal-title":"J Bone Miner Res"},{"key":"2024013019135583400_bib3","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1182\/blood.V87.2.518.bloodjournal872518","article-title":"Human osteoblasts support human hematopoietic progenitor cells in in vitro bone marrow cultures","volume":"87","author":"Taichman","year":"1996","journal-title":"Blood"},{"key":"2024013019135583400_bib4","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1359\/jbmr.2000.15.1.2","article-title":"The roles of osteoprotegerin and osteoprotegerin ligand in the paracrine regulation of bone resorption","volume":"15","author":"Hofbauer","year":"2000","journal-title":"J Bone Miner Res"},{"key":"2024013019135583400_bib5","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1182\/blood.V78.1.55.55","article-title":"Identification of stromal cell precursors in human bone marrow by a novel monoclonal antibody STRO-1","volume":"78","author":"Simmons","year":"1991","journal-title":"Blood"},{"key":"2024013019135583400_bib6","doi-asserted-by":"crossref","first-page":"4164","DOI":"10.1182\/blood.V84.12.4164.bloodjournal84124164","article-title":"The STRO-1+ fraction of adult human bone marrow contains the osteogenic precursors","volume":"84","author":"Gronthos","year":"1994","journal-title":"Blood"},{"key":"2024013019135583400_bib7","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1359\/jbmr.1999.14.1.47","article-title":"Differential cell surface expression of the STRO-1 and alkaline phosphatase antigens on discrete developmental stages in primary cultures of human bone cells","volume":"14","author":"Gronthos","year":"1999","journal-title":"J Bone Miner Res"},{"key":"2024013019135583400_bib8","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1359\/jbmr.1999.14.8.1345","article-title":"Further characterization of cells expressing STRO-1 in cultures of adult human bone marrow stromal cells","volume":"14","author":"Stewart","year":"1999","journal-title":"J Bone Miner Res"},{"key":"2024013019135583400_bib9","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1359\/jbmr.1999.14.3.351","article-title":"Isolation and characterization of human clonogenic osteoblast progenitors immunoselected from fetal bone marrow stroma using STRO-1 monoclonal antibody","volume":"14","author":"Oyajobi","year":"1999","journal-title":"J Bone Miner Res"},{"key":"2024013019135583400_bib10","first-page":"449","article-title":"Immunomagnetic isolation of osteoprogenitors from human bone marrow stroma","volume":"79","author":"Encina","year":"1999","journal-title":"Lab Invest"},{"key":"2024013019135583400_bib11","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1159\/000046182","article-title":"The STRO-1+ marrow cell population is multipotential","volume":"170","author":"Dennis","year":"2002","journal-title":"Cells Tissues Organs"},{"key":"2024013019135583400_bib12","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S8756-3282(00)80937-0","article-title":"The mechanism of coupling: A role for the vasculature","volume":"26","author":"Parfitt","year":"2000","journal-title":"Bone"},{"key":"2024013019135583400_bib13","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1146\/annurev.immunol.20.100301.064753","article-title":"RANK-L and RANK: T cells, bone loss, and mammalian evolution","volume":"20","author":"Theill","year":"2002","journal-title":"Annu Rev Immunol"},{"key":"2024013019135583400_bib14","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1006\/bbrc.1998.8610","article-title":"Osteoclast differentiation factor mediates an essential signal for bone resorption induced by 1 alpha, 25-dihydroxyvitamin D3, prostaglandin E2, or parathyroid hormone in the microenvironment of bone","volume":"246","author":"Tsukii","year":"1998","journal-title":"Biochem Biophys Res Commun"},{"key":"2024013019135583400_bib15","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0092-8674(00)81569-X","article-title":"Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation","volume":"93","author":"Lacey","year":"1998","journal-title":"Cell"},{"key":"2024013019135583400_bib16","doi-asserted-by":"crossref","first-page":"3597","DOI":"10.1073\/pnas.95.7.3597","article-title":"Osteoclast differentiation factor is a ligand for osteoprotegerin\/osteoclastogenesis-inhibitory factor and is identical to TRANCE\/RANKL","volume":"95","author":"Yasuda","year":"1998","journal-title":"Proc Natl Acad Sci USA"},{"key":"2024013019135583400_bib17","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/16852","article-title":"OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis","volume":"397","author":"Kong","year":"1999","journal-title":"Nature"},{"key":"2024013019135583400_bib18","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/S0092-8674(00)80209-3","article-title":"Osteoprotegerin: A novel secreted protein involved in the regulation of bone density","volume":"89","author":"Simonet","year":"1997","journal-title":"Cell"},{"key":"2024013019135583400_bib19","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1359\/jbmr.2001.16.6.1015","article-title":"The ratio of messenger RNA levels of receptor activator of nuclear factor kappaB ligand to osteoprotegerin correlates with bone remodeling indices in normal human cancellous bone but not in osteoarthritis","volume":"16","author":"Fazzalari","year":"2001","journal-title":"J Bone Miner Res"},{"key":"2024013019135583400_bib20","doi-asserted-by":"crossref","first-page":"4768","DOI":"10.1210\/endo.141.12.7840","article-title":"The expression of osteoprotegerin and RANK ligand and the support of osteoclast formation by stromal-osteoblast lineage cells is developmentally regulated","volume":"141","author":"Gori","year":"2000","journal-title":"Endocrinology"},{"key":"2024013019135583400_bib21","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1677\/joe.0.1700451","article-title":"Changing RANKL\/OPG mRNA expression in differentiating murine primary osteoblasts","volume":"170","author":"Thomas","year":"2001","journal-title":"J Endocrinol"},{"key":"2024013019135583400_bib22","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1210\/endo-125-4-1805","article-title":"The bone marrow-derived stromal cell lines MC3T3-G2\/PA6 and ST2 support osteoclast-like cell differentiation in cocultures with mouse spleen cells","volume":"125","author":"Udagawa","year":"1989","journal-title":"Endocrinology"},{"key":"2024013019135583400_bib23","doi-asserted-by":"crossref","first-page":"4058","DOI":"10.1210\/endo.137.9.8756585","article-title":"The human osteoclast precursor circulates in the monocyte fraction","volume":"137","author":"Fujikawa","year":"1996","journal-title":"Endocrinology"},{"key":"2024013019135583400_bib24","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/S8756-3282(99)00176-3","article-title":"Bidirectional signaling between stromal and hemopoietic cells regulates interleukin-1 expression during human osteoclast formation","volume":"25","author":"Haynes","year":"1999","journal-title":"Bone"},{"key":"2024013019135583400_bib25","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/S8756-3282(00)00280-5","article-title":"Coordinated cytokine expression by stromal and hematopoietic cells during human osteoclast formation","volume":"26","author":"Atkins","year":"2000","journal-title":"Bone"},{"key":"2024013019135583400_bib26","doi-asserted-by":"crossref","first-page":"4743","DOI":"10.1210\/endo.139.11.6433","article-title":"Osteotropic agents regulate the expression of osteoclast differentiation factor and osteoprotegerin in osteoblastic stromal cells","volume":"139","author":"Horwood","year":"1998","journal-title":"Endocrinology"},{"key":"2024013019135583400_bib27","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/S0167-4781(99)00032-9","article-title":"Promoter structure of mouse RANKL\/TRANCE\/OPGL\/ODF gene","volume":"1445","author":"Kitazawa","year":"1999","journal-title":"Biochim Biophys Acta"},{"key":"2024013019135583400_bib28","doi-asserted-by":"crossref","first-page":"4382","DOI":"10.1210\/endo.140.10.7034","article-title":"Stimulation of osteoprotegerin ligand and inhibition of osteoprotegerin production by glucocorticoids in human osteoblastic lineage cells: Potential paracrine mechanisms of glucocorticoid-induced osteoporosis","volume":"140","author":"Hofbauer","year":"1999","journal-title":"Endocrinology"},{"key":"2024013019135583400_bib29","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1002\/(SICI)1096-9896(199902)187:3<374::AID-PATH257>3.0.CO;2-V","article-title":"Osteoblastic differentiation and mRNA analysis of STRO-1-positive human bone marrow stromal cells using primary in vitro culture and poly (A) PCR","volume":"187","author":"Byers","year":"1999","journal-title":"J Pathol"},{"key":"2024013019135583400_bib30","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1089\/107632700300003323","article-title":"Differentiation of osteoblasts and in vitro bone formation from murine embryonic stem cells","volume":"7","author":"Buttery","year":"2001","journal-title":"Tissue Eng"},{"key":"2024013019135583400_bib31","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1093\/rheumatology\/40.1.74","article-title":"High concentrations of dexamethasone suppress the proliferation but not the differentiation or further maturation of human osteoblast precursors in vitro: Relevance to glucocorticoid-induced osteoporosis","volume":"40","author":"Walsh","year":"2001","journal-title":"Rheumatology"},{"key":"2024013019135583400_bib32","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/0022-1759(94)90236-4","article-title":"Determination of lymphocyte division by flow cytometry","volume":"171","author":"Lyons","year":"1994","journal-title":"J Immunol Methods"},{"key":"2024013019135583400_bib33","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1359\/jbmr.2000.15.4.640","article-title":"Expression of osteoclast differentiation signals by stromal elements of giant cell tumors","volume":"15","author":"Atkins","year":"2000","journal-title":"J Bone Miner Res"},{"key":"2024013019135583400_bib34","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1002\/jcp.1041430304","article-title":"Progressive development of the rat osteoblast phenotype in vitro: Reciprocal relationships in expression of genes associated with osteoblast proliferation and differentiation during formation of the bone extracellular matrix","volume":"143","author":"Owen","year":"1990","journal-title":"J Cell Physiol"},{"key":"2024013019135583400_bib35","first-page":"199","article-title":"Vitamin D control of osteoblast function and bone extracellular matrix mineralization","volume":"11","author":"van Leeuwen","year":"2001","journal-title":"Crit Rev Eukaryot Gene Expr"},{"key":"2024013019135583400_bib36","first-page":"299","article-title":"Regulation of osteoblast growth by interactions between transforming growth factor-beta and 1alpha, 25-dihydroxyvitamin D3","volume":"11","author":"Gurlek","year":"2001","journal-title":"Crit Rev Eukaryot Gene Expr"},{"key":"2024013019135583400_bib37","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1002\/(SICI)1097-4644(19991001)75:1<22::AID-JCB3>3.0.CO;2-6","article-title":"Development of the osteoblast phenotype in primary human osteoblasts in culture: Comparison with rat calvarial cells in osteoblast differentiation","volume":"75","author":"Siggelkow","year":"1999","journal-title":"J Cell Biochem"},{"key":"2024013019135583400_bib38","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1007\/PL00005823","article-title":"1, 25 dihydroxyvitamin-D3 attenuates the confluence-dependent differences in the osteoblast characteristic proteins alkaline phosphatase, procollagen I peptide, and osteocalcin","volume":"64","author":"Siggelkow","year":"1999","journal-title":"Calcif Tissue Int"},{"key":"2024013019135583400_bib39","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1210\/endo-128-3-1496","article-title":"Pleiotropic effects of vitamin D on osteoblast gene expression are related to the proliferative and differentiated state of the bone cell phenotype: Dependency upon basal levels of gene expression, duration of exposure, and bone matrix competency in normal rat osteoblast cultures","volume":"128","author":"Owen","year":"1991","journal-title":"Endocrinology"},{"key":"2024013019135583400_bib40","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S0039-128X(00)00200-2","article-title":"Vitamin D receptor and nuclear receptor coactivators: Crucial interactions in vitamin D-mediated transcription","volume":"66","author":"MacDonald","year":"2001","journal-title":"Steroids"},{"key":"2024013019135583400_bib41","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1677\/joe.0.1590191","article-title":"Osteoprotegerin mRNA is expressed in primary human osteoblast-like cells: Down-regulation by glucocorticoids","volume":"159","author":"Vidal","year":"1998","journal-title":"J Endocrinol"},{"key":"2024013019135583400_bib42","doi-asserted-by":"crossref","first-page":"4629","DOI":"10.1210\/endo.138.11.5511","article-title":"Short-term treatment of rats with high dose 1, 25-dihydroxyvitamin D3 stimulates bone formation and increases the number of osteoblast precursor cells in bone marrow","volume":"138","author":"Erben","year":"1997","journal-title":"Endocrinology"},{"key":"2024013019135583400_bib43","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1359\/jbmr.2002.17.8.1498","article-title":"Prevention of bone loss in ovariectomized rats by combined treatment with risedronate and 1, 25-dihydroxyvitamin D3","volume":"17","author":"Erben","year":"2002","journal-title":"J Bone Miner Res"},{"key":"2024013019135583400_bib44","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1096\/fj.99-1075com","article-title":"Increased formation and decreased resorption of bone in mice with elevated vitamin D receptor in mature cells of the osteoblastic lineage","volume":"14","author":"Gardiner","year":"2000","journal-title":"FASEB J"},{"key":"2024013019135583400_bib45","doi-asserted-by":"crossref","first-page":"3618","DOI":"10.1210\/jcem.86.8.7703","article-title":"Combination treatment with estrogen and calcitriol in the prevention of age-related bone loss","volume":"86","author":"Gallagher","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"2024013019135583400_bib46","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1172\/JCI0214538","article-title":"Promotion of osteoclast survival and antagonism of bisphosphonate-induced osteoclast apoptosis by glucocorticoids","volume":"109","author":"Weinstein","year":"2002","journal-title":"J Clin Invest"},{"key":"2024013019135583400_bib47","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1002\/jcb.10122","article-title":"Prolonged culture of HOS 58 human osteosarcoma cells with 1, 25-(OH)2-D3 TGF-beta, and dexamethasone reveals physiological regulation of alkaline phosphatase, dissociated osteocalcin gene expression, and protein synthesis and lack of mineralization","volume":"85","author":"Siggelkow","year":"2002","journal-title":"J Cell Biochem"},{"key":"2024013019135583400_bib48","doi-asserted-by":"crossref","first-page":"5681","DOI":"10.1210\/jcem.86.12.8066","article-title":"Glucocorticoid-induced osteoporosis: Summary of a workshop","volume":"86","author":"Canalis","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"2024013019135583400_bib49","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1359\/jbmr.1998.13.5.828","article-title":"Vascular pericytes express osteogenic potential in vitro and in vivo","volume":"13","author":"Doherty","year":"1998","journal-title":"J Bone Miner Res"}],"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.2003.18.6.1088","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/18\/6\/1088\/56470386\/5650180618.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/18\/6\/1088\/56470386\/5650180618.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T15:07:12Z","timestamp":1710342432000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/18\/6\/1088-1098\/7592423"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,6,1]]},"references-count":49,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2009,12,2]]},"published-print":{"date-parts":[[2003,6,1]]}},"URL":"https:\/\/doi.org\/10.1359\/jbmr.2003.18.6.1088","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2003,6,1]]},"published":{"date-parts":[[2003,6,1]]}}}