{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T03:21:31Z","timestamp":1780456891515,"version":"3.54.1"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2004,3,1]],"date-time":"2004-03-01T00:00:00Z","timestamp":1078099200000},"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":[[2004,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Primary cultures of bovine parathyroid cells rapidly lose calcium responsiveness. Here, we show that bovine parathyroid cells grown in collagen coalesce into an organoid (\u201cpseudogland\u201d) with stable calcium responsiveness. These findings also illustrate the importance of 3-D cellular architecture in parathyroid gland function.<\/jats:p>\n               <jats:p>Introduction: The ability of extracellular calcium to suppress parathyroid hormone (PTH) secretion is quickly lost in primary monolayer cultures of bovine parathyroid cells. This has been attributed to a decrease in the expression of the cell surface calcium-sensing receptor (CaR), but other factors, including normal cell-to-cell interaction, may be critical. Here we describe a novel system for culturing bovine parathyroid cells that promotes re-formation of a three-dimensional (3-D) cellular architecture and re-establishment of calcium responsiveness.<\/jats:p>\n               <jats:p>Materials and Methods: Dispersed bovine parathyroid cells were cultured as monolayers or were mixed with type I collagen and placed in culture plates. CaR mRNA and the calcium regulation of PTH secretion were measured over a period of several weeks in parathyroid cells cultured both in collagen matrix and as monolayers. Calcium regulation of PTH mRNA was also investigated.<\/jats:p>\n               <jats:p>Results and Conclusions: Within 1\u20132 weeks in collagen culture, parathyroid cells coalesced into a small mass approximately 1\u20132 mm in size (referred to as a pseudogland). Suppression of PTH secretion by high calcium was blunted at 1 day in collagen, but returned within 1 week, and was retained through 3 weeks; the calcium set point (1.05 \u00b1 0.04 mM) was similar to that reported for freshly dispersed cells. PTH mRNA was also suppressed by increasing extracellular calcium. CaR mRNA expression was decreased at 1 day in collagen and increased with time in culture, although never reaching the level found in dispersed cells. In bovine parathyroid cells cultured as monolayers, however, suppression of PTH by calcium was observed only at day 1 in culture. CaR mRNA content fell by 70% at day 1 but remained stable thereafter. Thus, a total loss of calcium responsiveness in monolayers was observed despite significant residual expression of CaR, suggesting that loss of the calcium response cannot be attributed solely to decreased CaR. In summary, the pseudogland model illustrates the importance of the 3-D cellular architecture in parathyroid gland function and provides a useful model in which to investigate calcium-mediated control of parathyroid gland functions, especially those requiring extended treatment.<\/jats:p>","DOI":"10.1359\/jbmr.2004.19.3.491","type":"journal-article","created":{"date-parts":[[2006,4,27]],"date-time":"2006-04-27T07:01:13Z","timestamp":1146121273000},"page":"491-498","source":"Crossref","is-referenced-by-count":27,"title":["Parathyroid Cells Cultured in Collagen Matrix Retain Calcium Responsiveness: Importance of Three-Dimensional Tissue Architecture"],"prefix":"10.1093","volume":"19","author":[{"given":"Cynthia S","family":"Ritter","sequence":"first","affiliation":[{"name":"Renal Division, Washington University School of Medicine, St Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Slatopolsky","sequence":"additional","affiliation":[{"name":"Renal Division, Washington University School of Medicine, St Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Santoro","sequence":"additional","affiliation":[{"name":"Renal Division, Washington University School of Medicine, St Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex J","family":"Brown","sequence":"additional","affiliation":[{"name":"Renal Division, Washington University School of Medicine, St Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,12,2]]},"reference":[{"key":"2024013019213712400_bib1","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/366575a0","article-title":"Cloning and characterization of an extracellular Ca2+-sensing receptor from bovine parathyroid","volume":"366","author":"Brown","year":"1993","journal-title":"Nature"},{"key":"2024013019213712400_bib2","first-page":"289","article-title":"The calcium-sensing receptor- a window into the physiology and pathophysiology of mineral ion metabolism","volume":"17","author":"Chattopadhyay","year":"1996","journal-title":"Endocr Rev"},{"key":"2024013019213712400_bib3","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1006\/bbrc.1995.2048","article-title":"Loss of calcium responsiveness in cultured bovine parathyroid cells is associated with decreased calcium receptor expression","volume":"212","author":"Brown","year":"1995","journal-title":"Biochem Biophys Res Commun"},{"key":"2024013019213712400_bib4","doi-asserted-by":"crossref","first-page":"3087","DOI":"10.1210\/endo.136.7.7789335","article-title":"The reduced responsiveness of cultured bovine parathyroid cells to extracellular Ca2+ is associated with marked reduction in the expression of extracellular Ca2+-sensing receptor messenger ribonucleic acid and protein","volume":"136","author":"Mithal","year":"1995","journal-title":"Endocrinology"},{"key":"2024013019213712400_bib5","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/BF02623538","article-title":"Characteristics of bovine parathyroid cell organoids in culture","volume":"22","author":"Ridgeway","year":"1986","journal-title":"In Vitro Cell Dev Biol"},{"key":"2024013019213712400_bib6","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1359\/jbmr.1998.13.3.354","article-title":"Persistence of Ca2+-sensing receptor expression in functionally active, long-term human parathyroid cell cultures","volume":"13","author":"Roussanne","year":"1998","journal-title":"J Bone Miner Res"},{"key":"2024013019213712400_bib7","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1097\/01.ASN.0000018148.50109.C0","article-title":"Clonal chromosomal defects in the molecular pathogenesis of refractory hyperparathyroidism of uremia","volume":"13","author":"Imanishi","year":"2002","journal-title":"J Am Soc Nephrol"},{"key":"2024013019213712400_bib8","doi-asserted-by":"crossref","first-page":"2534","DOI":"10.1172\/JCI118701","article-title":"Phosphorus restriction prevents parathyroid gland growth-high phosphorus directly stimulates PTH secretion in vitro","volume":"97","author":"Slatopolsky","year":"1996","journal-title":"J Clin Invest"},{"key":"2024013019213712400_bib9","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1093\/oxfordjournals.ndt.a027665","article-title":"A direct effect in vitro of phosphate on PTH release from bovine parathyroid tissue slices but not from dispersed parathyroid cells","volume":"11","author":"Nielsen","year":"1996","journal-title":"Nephrol Dial Transplant"},{"key":"2024013019213712400_bib10","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1002\/jbmr.5650110714","article-title":"Direct effect of phosphorus on PTH secretion from whole rat parathyroid glands in vitro","volume":"11","author":"Almaden","year":"1996","journal-title":"J Bone Miner Res"},{"key":"2024013019213712400_bib11","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1002\/ijc.2910440324","article-title":"Integrin-receptor-mediated differentiation and growth inhibition are enhanced by transforming growth factor b in colorectal tumour cells grown in collagen gel","volume":"44","author":"Pignatelli","year":"1989","journal-title":"Int J Cancer"},{"key":"2024013019213712400_bib12","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1242\/jcs.108.2.595","article-title":"Alteration of collagen-dependent adhesion, motility, and morphogenesis by the expression of antisense alpha 2 integrin mRNA in mammary cells","volume":"108","author":"Keely","year":"1995","journal-title":"J Cell Sci"},{"key":"2024013019213712400_bib13","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1006\/excr.1993.1286","article-title":"The effect of three dimensional collagen type I preparation on the structural organization of guinea pig enteric ganglia in culture","volume":"209","author":"Bergsteinsdottir","year":"1993","journal-title":"Exp Cell Res"},{"key":"2024013019213712400_bib14","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1002\/jcp.1041610303","article-title":"Glandular-like morphogenesis and secretory activity of human trachael gland cells in a three-dimensional collagen gel matrix","volume":"161","author":"Jacquot","year":"1994","journal-title":"J Cell Physiol"},{"key":"2024013019213712400_bib15","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1046\/j.1440-1827.2001.01218.x","article-title":"Thyrocyte integration, thyroid folliculogenesis and tissue regeneration: Perspective for thyroid tissue engineering","volume":"51","author":"Toda","year":"2001","journal-title":"Pathol Int"},{"key":"2024013019213712400_bib16","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1210\/endo.130.1.1309332","article-title":"Binding and metabolism of 1,25-dihydroxyvitamin D3 in cultured bovine parathyroid cells","volume":"130","author":"Brown","year":"1992","journal-title":"Endocrinology"},{"key":"2024013019213712400_bib17","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1172\/JCI108077","article-title":"Metabolism of immunoreactive parathyroid hormone in the dog. The role of the kidney and the effects of chronic renal failure","volume":"56","author":"Hruska","year":"1975","journal-title":"J Clin Invest"},{"key":"2024013019213712400_bib18","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/0003-2697(66)90012-1","article-title":"A new fluorometric method for RNA and DNA determination","volume":"17","author":"Le Pecq","year":"1966","journal-title":"Anal Biochem"},{"key":"2024013019213712400_bib19","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/0303-7207(82)90136-8","article-title":"Nucleotide sequence of bovine parathyroid hormone messenger RNA","volume":"28","author":"Weaver","year":"1982","journal-title":"Mol Cell Endocrinol"},{"key":"2024013019213712400_bib20","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1046\/j.1523-1755.1999.00386.x","article-title":"Decreased calcium-sensing receptor expression in hyperplastic parathyroid glands of uremic rats: Role of dietary phosphate","volume":"55","author":"Brown","year":"1999","journal-title":"Kidney Int"},{"key":"2024013019213712400_bib21","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1159\/000057471","article-title":"Transcriptional and post-transcriptional regulation of PTH gene expression by vitamin D, calcium and phosphate","volume":"25","author":"Sela-Brown","year":"1999","journal-title":"Min Electrol Metab"},{"key":"2024013019213712400_bib22","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1023\/A:1026570518919","article-title":"Calcium receptor and regulation of parathyroid hormone secretion","volume":"1","author":"Brown","year":"2000","journal-title":"Rev Endocr Metab Disord"},{"key":"2024013019213712400_bib23","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1172\/JCI111696","article-title":"Regulation of parathyroid hormone release and cytosolic calcium by extracellular calcium in dispersed and cultured bovine and pathological human parathyroid cells","volume":"75","author":"LeBoff","year":"1985","journal-title":"J Clin Invest"},{"key":"2024013019213712400_bib24","doi-asserted-by":"crossref","first-page":"2398","DOI":"10.1093\/ndt\/14.10.2398","article-title":"The PTH-calcium curve and the set point of calcium in primary and secondary hyperparathyroidism","volume":"14","author":"Malberti","year":"1999","journal-title":"Nephrol Dial Transplant"},{"key":"2024013019213712400_bib25","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/0167-4889(88)90014-6","article-title":"Modulation of the Ca2+-sensing function of parathyroid cells in vitro and in hyperparathyroidism","volume":"968","author":"Nygren","year":"1988","journal-title":"Biochim Biophys Acta"}],"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.2004.19.3.491","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/19\/3\/491\/56475207\/5650190318.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/19\/3\/491\/56475207\/5650190318.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T15:07:54Z","timestamp":1710342474000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/19\/3\/491-498\/7592839"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,3,1]]},"references-count":25,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2009,12,2]]},"published-print":{"date-parts":[[2004,3,1]]}},"URL":"https:\/\/doi.org\/10.1359\/jbmr.2004.19.3.491","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2004,3,1]]},"published":{"date-parts":[[2004,3,1]]}}}