{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:04:43Z","timestamp":1790161483716,"version":"4.1.0"},"reference-count":29,"publisher":"The Endocrine Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We have examined the role of PTH in the postnatal state in a mouse model of PTH deficiency generated by targeting the Pth gene in embryonic stem cells. Mice homozygous for the ablated allele, when maintained on a normal calcium intake, developed hypocalcemia, hyperphosphatemia, and low circulating 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] levels consistent with primary hypoparathyroidism. Bone turnover was reduced, leading to increased trabecular and cortical bone volume in PTH-deficient mice. When mutant mice were placed on a low-calcium diet, renal 25-hydroxyvitamin D 1 \u03b1-hydroxylase expression increased despite the absence of PTH, leading to a rise in circulating 1,25(OH)2D3 levels, marked osteoclastogenesis, and profound bone resorption. These studies demonstrate the dependence of the skeletal phenotype in animals with genetically depleted PTH on the external environment as well as on internal hormonal and ionic circulatory factors. They also show that, although PTH action is the first defense against hypocalcemia, 1,25(OH)2D3 can be mobilized, even in the absence of PTH, to guard against extreme calcium deficiency.<\/jats:p>","DOI":"10.1210\/en.2003-1097","type":"journal-article","created":{"date-parts":[[2004,1,6]],"date-time":"2004-01-06T01:13:08Z","timestamp":1073351588000},"page":"2046-2053","source":"Crossref","is-referenced-by-count":81,"title":["Skeletal Abnormalities in Pth-Null Mice Are Influenced by Dietary Calcium"],"prefix":"10.1210","volume":"145","author":[{"given":"Dengshun","family":"Miao","sequence":"first","affiliation":[{"name":"Calcium Research Laboratory and Department of Medicine (D.M., G.N.H., D.G.), McGill University Health Centre and Royal Victoria Hospital, McGill University, Montreal, Canada H3A 1A1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"He","sequence":"additional","affiliation":[{"name":"Department of Medicine and Lady Davis Institute for Medical Research (B.H., X.-Y.B., X.-K.T., A.C.K.), Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal, Canada H3T 1E2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beate","family":"Lanske","sequence":"additional","affiliation":[{"name":"Department of Oral and Developmental Biology (B.L.), Forsyth Institute and Harvard School of Dental Medicine, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu-Ying","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Medicine and Lady Davis Institute for Medical Research (B.H., X.-Y.B., X.-K.T., A.C.K.), Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal, Canada H3T 1E2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-Kang","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Medicine and Lady Davis Institute for Medical Research (B.H., X.-Y.B., X.-K.T., A.C.K.), Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal, Canada H3T 1E2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey N.","family":"Hendy","sequence":"additional","affiliation":[{"name":"Calcium Research Laboratory and Department of Medicine (D.M., G.N.H., D.G.), McGill University Health Centre and Royal Victoria Hospital, McGill University, Montreal, Canada H3A 1A1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Goltzman","sequence":"additional","affiliation":[{"name":"Calcium Research Laboratory and Department of Medicine (D.M., G.N.H., D.G.), McGill University Health Centre and Royal Victoria Hospital, McGill University, Montreal, Canada H3A 1A1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew C.","family":"Karaplis","sequence":"additional","affiliation":[{"name":"Department of Medicine and Lady Davis Institute for Medical Research (B.H., X.-Y.B., X.-K.T., A.C.K.), Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal, Canada H3T 1E2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071618162563600_R1","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1126\/science.1658941","article-title":"A G protein-linked receptor for parathyroid hormone and parathyroid hormone-related peptide.","volume":"254","author":"Juppner","year":"1991","journal-title":"Science"},{"key":"2020071618162563600_R2","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.1210\/endo.132.5.8386612","article-title":"Identical complementary deoxyribonucleic acids encode a human renal and bone parathyroid hormone (PTH)\/PTH-related peptide receptor.","volume":"132","author":"Schipani","year":"1993","journal-title":"Endocrinology"},{"key":"2020071618162563600_R3","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S0065-3233(08)60471-4","article-title":"Parathyroid hormone: chemistry, biosynthesis, and mode of action.","volume":"35","author":"Potts Jr","year":"1982","journal-title":"Adv Protein Chem"},{"key":"2020071618162563600_R4","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1056\/NEJM200001203420306","article-title":"The physiology of parathyroid hormone-related protein.","volume":"342","author":"Strewler","year":"2000","journal-title":"N Engl J Med"},{"key":"2020071618162563600_R5","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1101\/gad.8.3.277","article-title":"Lethal skeletal dysplasia from targeted disruption of the parathyroid hormone-related peptide gene.","volume":"8","author":"Karaplis","year":"1994","journal-title":"Genes Dev"},{"key":"2020071618162563600_R6","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1126\/science.273.5275.663","article-title":"PTH\/PTHrP receptor in early development and Indian hedgehog-regulated bone growth.","volume":"273","author":"Lanske","year":"1996","journal-title":"Science"},{"key":"2020071618162563600_R7","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1172\/JCI2918","article-title":"Absence of functional receptors for parathyroid hormone and parathyroid hormone-related peptide in Blomstrand chondrodysplasia.","volume":"102","author":"Jobert","year":"1998","journal-title":"J Clin Invest"},{"key":"2020071618162563600_R8","doi-asserted-by":"crossref","first-page":"5255","DOI":"10.1210\/endo.139.12.6522","article-title":"Inactivating mutation in the human parathyroid hormone receptor type 1 gene in Blomstrand chondrodysplasia.","volume":"139","author":"Karaplis","year":"1998","journal-title":"Endocrinology"},{"key":"2020071618162563600_R9","doi-asserted-by":"crossref","first-page":"3363","DOI":"10.1210\/endo.140.7.6855","article-title":"Distribution of the parathyroid hormone 2 receptor in rat: immunolocalization reveals expression by several endocrine cells.","volume":"140","author":"Usdin","year":"1999","journal-title":"Endocrinology"},{"key":"2020071618162563600_R10","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/S0165-6147(00)01455-3","article-title":"The PTH2 receptor and TIP39: a new peptide-receptor system.","volume":"21","author":"Usdin","year":"2000","journal-title":"Trends Pharmacol Sci"},{"key":"2020071618162563600_R11","doi-asserted-by":"crossref","first-page":"4732","DOI":"10.1210\/endo.136.11.7588200","article-title":"Characterization of a novel parathyroid hormone (PTH) receptor with specificity for the carboxyl-terminal region of PTH-(1\u201384).","volume":"136","author":"Inomata","year":"1995","journal-title":"Endocrinology"},{"key":"2020071618162563600_R12","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1210\/endo.142.2.7955","article-title":"Receptors for the carboxyl-terminal region of pth(1\u201384) are highly expressed in osteocytic cells.","volume":"142","author":"Divieti","year":"2001","journal-title":"Endocrinology"},{"key":"2020071618162563600_R13","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1172\/JCI0214817","article-title":"Parathyroid hormone is essential for normal fetal bone formation.","volume":"109","author":"Miao","year":"2002","journal-title":"J Clin Invest"},{"key":"2020071618162563600_R14","doi-asserted-by":"crossref","first-page":"2913","DOI":"10.1210\/me.2002-0113","article-title":"Partial rescue of the Hyp phenotype by osteoblast-targeted PHEX (phosphate-regulating gene with homologies to endopeptidases on the X chromosome) expression.","volume":"16","author":"Bai","year":"2002","journal-title":"Mol Endocrinol"},{"key":"2020071618162563600_R15","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/35018111","article-title":"Genetic ablation of parathyroid glands reveals another source of parathyroid hormone.","volume":"406","author":"Gunther","year":"2000","journal-title":"Nature"},{"key":"2020071618162563600_R16","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1093\/jn\/131.6.1787","article-title":"Vitamin D receptor null mutant mice fed high levels of calcium are fertile.","volume":"131","author":"Johnson","year":"2001","journal-title":"J Nutr"},{"key":"2020071618162563600_R17","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1136\/bmj.291.6500.955","article-title":"Prolonged hypoparathyroidism presenting eventually as second trimester abortion.","volume":"291","author":"Eastell","year":"1985","journal-title":"BMJ"},{"key":"2020071618162563600_R18","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1210\/jcem-26-5-487","article-title":"Intrauterine hyperparathyroidism: a complication of untreated maternal hypoparathyroidism.","volume":"26","author":"Aceto","year":"1966","journal-title":"J Clin Endocrinol"},{"key":"2020071618162563600_R19","doi-asserted-by":"crossref","first-page":"3155","DOI":"10.1210\/jc.2002-021388","article-title":"Increased bone mineral density in patients with chronic hypoparathyroidism.","volume":"88","author":"Chan","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071618162563600_R20","first-page":"1617","article-title":"Bone mineral density in patients with chronic hypoparathyroidism.","volume":"76","author":"Abugassa","year":"1993","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071618162563600_R21","first-page":"2135","article-title":"Attenuation of postmenopausal high turnover bone loss in patients with hypoparathyroidism.","volume":"80","author":"Fujiyama","year":"1995","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071618162563600_R22","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1136\/pgmj.66.782.1061","article-title":"High peripheral and axial bone densities in a postmenopausal woman with untreated hypoparathyroidism.","volume":"66","author":"Orr-Walker","year":"1990","journal-title":"Postgrad Med J"},{"key":"2020071618162563600_R23","first-page":"64","article-title":"High bone mass and hypocalcaemic myopathy in a patient with idiopathic hypoparathyroidism.","volume":"19","author":"Van Offel","year":"2000","journal-title":"Clin Rheumatol"},{"key":"2020071618162563600_R24","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S8756-3282(99)00263-X","article-title":"Daily intermittent decreases in serum levels of parathyroid hormone have an anabolic-like action on the bones of uremic rats with low-turnover bone and osteomalacia.","volume":"26","author":"Ishii","year":"2000","journal-title":"Bone"},{"key":"2020071618162563600_R25","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1146\/annurev.med.52.1.203","article-title":"Prevention of uremic bone disease using calcimimetic compounds.","volume":"52","author":"Olgaard","year":"2001","journal-title":"Annu Rev Med"},{"key":"2020071618162563600_R26","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/S8756-3282(00)00350-1","article-title":"Daily transient decreases in plasma parathyroid hormone levels induced by the calcimimetic NPS R-568 slows the rate of bone loss but does not increase bone mass in ovariectomized rats.","volume":"27","author":"Miller","year":"2000","journal-title":"Bone"},{"key":"2020071618162563600_R27","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":"2020071618162563600_R28","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1002\/jbmr.5650040618","article-title":"Regulation of 1,25-dihydroxyvitamin D3 by calcium in the parathyroidectomized, parathyroid hormone-replete rat.","volume":"4","author":"Weisinger","year":"1989","journal-title":"J Bone Miner Res"},{"key":"2020071618162563600_R29","doi-asserted-by":"crossref","first-page":"2027","DOI":"10.1210\/endo.140.5.6683","article-title":"Constitutive expression of 25-hydroxyvitamin D3\u20131\u03b1-hydroxylase in a transformed human proximal tubule cell line: evidence for direct regulation of vitamin D metabolism by calcium.","volume":"140","author":"Bland","year":"1999","journal-title":"Endocrinology"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/145\/4\/2046\/10788088\/endo2046.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/145\/4\/2046\/10788088\/endo2046.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T03:49:07Z","timestamp":1594957747000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/145\/4\/2046\/2879214"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,4,1]]},"references-count":29,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2004,4,1]]}},"URL":"https:\/\/doi.org\/10.1210\/en.2003-1097","relation":{},"ISSN":["0013-7227","1945-7170"],"issn-type":[{"value":"0013-7227","type":"print"},{"value":"1945-7170","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,4,1]]}}}