{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T20:42:26Z","timestamp":1780692146267,"version":"3.54.1"},"reference-count":70,"publisher":"Wiley","issue":"s1","license":[{"start":{"date-parts":[[2005,8,17]],"date-time":"2005-08-17T00:00:00Z","timestamp":1124236800000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Ther Apher Dial"],"published-print":{"date-parts":[[2005,8]]},"abstract":"<jats:p><jats:bold>Abstract:\u2002<\/jats:bold> The parathyroid gland (PTG) is a unique endocrine organ in which the quiescent glandular cells begin to proliferate in rsponse to the demand for maintaining calcium (Ca) homeostasis in the progressive course of renal failure, leading to secondary hypereparathyroidism (SHPT). SHPT is characterized with continuous over\u2010secretion of parathyroid hormone (PTH) and high turn\u2010over bone disease, osteitis fibrosa, and the major factors include a deficiency of active vitamin D, hypocalcemia, and phosphate retention. With long\u2010term end\u2010stage renal failure, SHPT becomes resistant to conventional medical treatment such as phosphate binders and active vitamin D supplementation, and the growth of the PTG accelerates with the pattern of hyperplasia changing from diffuse to nodular type. In this process, the sigmoid curve between extracellular Ca concentration (exCa) and the plasma level of PTH shifts to the upper\u2010rightward, indicating both an absolute increase in PTH secretion and the resistance of PT cells to exCa. Many experimental and human studies have revealed down\u2010regulation of vitamin D receptor (VDR), calcium\u2010sensing receptor (CaSR), and retinoid X receptor (RXR) in PT cells. The sustained proliferation of PT cells after obtaining autonomicity is another characteristic feature of SHPT. In this context, it has been demonstrated that the cell cycle is markedly progressed, where the expression of cyclin\u2010dependent kinase inhibitor (CDKI), p21 and p27, is depressed in a VDR\u2010dependent manner. These pathological features are most evident in nodular hyperplasia, in which monoclonal proliferation is obvious, indicating the phenotypic changes have occured in PT cells. It has been observed by Fukagawa and colleagues that pharmacologically high dose of active vitamin D administered orally can cause small\u2010size PTG hyperplasia to regress in patients with advanced SHPT. Successful renal transplantation may also restore VDR and CaSR expressions in the diffuse type, in association with increasing TUNEL\u2010positive cells. Thus, it is important to vigorously treat SHPT when the PT cell proliferation is in the reversible stage of diffuse hyperplasia.<\/jats:p>","DOI":"10.1111\/j.1744-9987.2005.00302.x","type":"journal-article","created":{"date-parts":[[2005,8,17]],"date-time":"2005-08-17T07:15:45Z","timestamp":1124262945000},"source":"Crossref","is-referenced-by-count":21,"title":["Parathyroid Cell Growth in Patients with Advanced Secondary Hyperparathyroidism: Vitamin D Receptor, Calcium Sensing Receptor, and Cell Cycle Regulating Factors"],"prefix":"10.1111","volume":"9","author":[{"given":"Masanori","family":"Tokumoto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatomo","family":"Taniguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dai","family":"Matsuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiko","family":"Tsuruya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Hirakata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuo","family":"Iida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,8,17]]},"reference":[{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1990.187"},{"key":"e_1_2_10_3_2","first-page":"293","volume-title":"The Parathyroids Basic and Clinical Concepts","author":"Parfitt AM","year":"2001"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0272-6386(95)90541-3"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/00041552-199307000-00006"},{"key":"e_1_2_10_6_2","first-page":"1299","volume-title":"Clinical Disorders of Fluid and Electrolyte Metabolism","author":"Coburn JW","year":"1994"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2002.kid585.x"},{"key":"e_1_2_10_8_2","first-page":"460A","article-title":"Diminished cyclin\u2010dependent kinase inhibitor (CDKI) as a main stream to parathyroid gland (PTG) hyperplasia linking with down\u2010regulation of calcium sensing receptor (CaSR)","volume":"14","author":"Tokumoto M","year":"2003","journal-title":"J Am Soc Nephrol"},{"key":"e_1_2_10_9_2","first-page":"34A","article-title":"Diminished expression of retinoid X receptor (RXR) \u2010\u03b1 links with the reduced expression of vitamin D receptor (VDR), p21, and p27 in the parathyroid (PT) glands of secondary hyperparathyroidism (2HPT)","volume":"15","author":"Tokumoto M","year":"2004","journal-title":"J Am Soc Nephrol"},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI111639"},{"key":"e_1_2_10_11_2","doi-asserted-by":"publisher","DOI":"10.1159\/000188261"},{"key":"e_1_2_10_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02067331"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2388(199703\/04)13:2<78::AID-SSU3>3.0.CO;2-Z"},{"key":"e_1_2_10_14_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.83.8.2765"},{"key":"e_1_2_10_15_2","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.1998.13.3.325"},{"key":"e_1_2_10_16_2","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.1996.0450"},{"key":"e_1_2_10_17_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1998.78.4.1193"},{"key":"e_1_2_10_18_2","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.1997.12.5.715"},{"key":"e_1_2_10_19_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2001.280.2.F291"},{"key":"e_1_2_10_20_2","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1681\/ASN.V133693","article-title":"Regulation of arachidonic acid production by intracellular calcium in parathyroid cells: effect of extracellular phosphate","volume":"13","author":"Almaden Y","year":"2002","journal-title":"J Am Soc Nephrol"},{"key":"e_1_2_10_21_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.130.3.1339"},{"key":"e_1_2_10_22_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.63.s85.4.x"},{"key":"e_1_2_10_23_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198706183162504"},{"key":"e_1_2_10_24_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116720"},{"key":"e_1_2_10_25_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.85.5.2000"},{"key":"e_1_2_10_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1987.216"},{"key":"e_1_2_10_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1989.3"},{"key":"e_1_2_10_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1996.283"},{"key":"e_1_2_10_29_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2004030236"},{"key":"e_1_2_10_30_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1999.00386.x"},{"key":"e_1_2_10_31_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2001.00027.x"},{"key":"e_1_2_10_32_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.81.4.1598"},{"key":"e_1_2_10_33_2","first-page":"S387","article-title":"The calcium receptor agonist NPS R\u2010568 suppresses PTH mRNA levels in cultured bovine parathyroid cells (Abstract)","volume":"10","author":"Garrett JE","year":"1995","journal-title":"J Bone Miner Res"},{"key":"e_1_2_10_34_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119851"},{"key":"e_1_2_10_35_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2000.00370.x"},{"key":"e_1_2_10_36_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1999.00396.x"},{"key":"e_1_2_10_37_2","first-page":"325","article-title":"DNA ploidy pattern of parathyroid parenchymal cells in renal secondary hyperparathyroidism","volume":"3","author":"Tominaga Y","year":"1991","journal-title":"Anal Cell Pathol"},{"key":"e_1_2_10_38_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00353781"},{"key":"e_1_2_10_39_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2001.059003855.x"},{"key":"e_1_2_10_40_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2004.01995.x"},{"key":"e_1_2_10_41_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199008093230617"},{"key":"e_1_2_10_42_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo-125-2-935"},{"key":"e_1_2_10_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1989.89"},{"key":"e_1_2_10_44_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1797.1997.tb00227.x"},{"key":"e_1_2_10_45_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.10.2.142"},{"key":"e_1_2_10_46_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2001.00042.x"},{"key":"e_1_2_10_47_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114840"},{"key":"e_1_2_10_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)88668-4"},{"key":"e_1_2_10_49_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118061"},{"key":"e_1_2_10_50_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.9.5253"},{"key":"e_1_2_10_51_2","first-page":"259","article-title":"Effect of calcium depletion on the rat parathyroids","volume":"3","author":"Svensson O","year":"1998","journal-title":"Bone Miner"},{"key":"e_1_2_10_52_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1699-0463.1991.tb01306.x"},{"key":"e_1_2_10_53_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118224"},{"key":"e_1_2_10_54_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1994.2515"},{"key":"e_1_2_10_55_2","doi-asserted-by":"crossref","first-page":"24554","DOI":"10.1016\/S0021-9258(18)35800-9","article-title":"Acidic fibroblast growth factor autocrine system as a mediator of calcium\u2010regulated parathyroid cell growth","volume":"267","author":"Sakaguchi K","year":"1992","journal-title":"J Biol Chem"},{"key":"e_1_2_10_56_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.5650050810"},{"key":"e_1_2_10_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1997.41"},{"key":"e_1_2_10_58_2","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1681\/ASN.V115903","article-title":"Activation of the calcium receptor by a calcimimetic compound halts the progression of secondary hyperparathyroidism in uremic rats","volume":"11","author":"Chin J","year":"2000","journal-title":"J Am Soc Nephrol"},{"key":"e_1_2_10_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90617-Y"},{"key":"e_1_2_10_60_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119359"},{"key":"e_1_2_10_61_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199610103351505"},{"key":"e_1_2_10_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1295-389"},{"key":"e_1_2_10_63_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.12.8.1193"},{"key":"e_1_2_10_64_2","doi-asserted-by":"crossref","first-page":"F454","DOI":"10.1152\/ajprenal.1996.270.3.F454","article-title":"Rat calcium\u2010sensing receptor is regulated by vitamin D but not by calcium","volume":"270","author":"Brown AJ","year":"1996","journal-title":"Am J Physiol-Renal"},{"key":"e_1_2_10_65_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M201804200"},{"key":"e_1_2_10_66_2","first-page":"136","article-title":"Molecular mechanism of the vitamin d\u2010induced progression of parathyroid gland hyperplasia in uremic rats fed high phosphorus diet: restoration of the expressions of vitamin D receptor, calcium sensing receptor and p21","volume":"18","author":"Taniguchi M","year":"2003","journal-title":"Nephrol Dial Transplant"},{"key":"e_1_2_10_67_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10523"},{"key":"e_1_2_10_68_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1994.223"},{"key":"e_1_2_10_69_2","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1093\/jn\/107.10.1918","article-title":"Response of chick parathyroid glands to the vitamin D metabolite 1,25\u2010cholecalciferol","volume":"107","author":"Henry HL","year":"1977","journal-title":"J Nutr"},{"key":"e_1_2_10_70_2","first-page":"276A","article-title":"Up\u2010regulation of both Ca\u2010sensing receptor (CaSR) and vitamin D receptor (VDR) in diffuse hyperplastic parathyroid glands after renal transplantayion (RTx) (Abstract)","volume":"15","author":"Taniguchi M","year":"2004","journal-title":"J Am Soc Nephrol"},{"key":"e_1_2_10_71_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2003.00154.x"}],"container-title":["Therapeutic Apheresis and Dialysis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1744-9987.2005.00302.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1744-9987.2005.00302.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T06:27:57Z","timestamp":1695796077000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1744-9987.2005.00302.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,8]]},"references-count":70,"journal-issue":{"issue":"s1","published-print":{"date-parts":[[2005,8]]}},"alternative-id":["10.1111\/j.1744-9987.2005.00302.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1744-9987.2005.00302.x","archive":["Portico"],"relation":{},"ISSN":["1744-9979","1744-9987"],"issn-type":[{"value":"1744-9979","type":"print"},{"value":"1744-9987","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,8]]}}}