{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T10:00:42Z","timestamp":1780480842293,"version":"3.54.1"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2005,10,1]],"date-time":"2005-10-01T00:00:00Z","timestamp":1128124800000},"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":[[2005,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We examined the effect of NH2-terminal fragments of PTHrP and PTH in young mutant mice deficient in both PTH and 1,25-dihydroxyvitamin D. Both proteins prolonged murine survival by increasing serum calcium, apparently by enhancing renal calcium transporter expression. The dominant effect on the skeleton was an increase in both endochondral bone and appositional formation without increased bone resorption.<\/jats:p>\n               <jats:p>Introduction: PTH-related protein (PTHrP) was discovered as a hypercalcemic agent responsible for the syndrome of humeral hypercalcemia of malignancy, and PTH is the major protein hormone regulating calcium homeostasis. Both proteins have skeletal anabolic actions when administered intermittently. We examined effects of exogenous PTHrP(1-86) and PTH(1-34) in double null mutant mice deficient in both PTH and 25-hydroxyvitamin D-1\u03b1-hydroxylase {1\u03b1(OH)ase} to determine the action of these proteins in the absence of the two major regulators of calcium and skeletal homeostasis.<\/jats:p>\n               <jats:p>Materials and Methods: Mice heterozygous for the PTH null allele and for the 1\u03b1(OH)ase null allele were mated to generate pups homozygous for both null alleles. PTHrP(1-86) and PTH(1-34) were administered subcutaneously starting 4 days after birth. Serum biochemistry and skeletal radiology, histology, and histomorphometry were performed, and indices of bone formation, resorption, and renal calcium transport were determined by real time RT-PCR, Western blot, and immunohistochemical approaches.<\/jats:p>\n               <jats:p>Results: In the double mutant mice, which die within 3 weeks after birth with severe hypocalcemia, tetany, and skeletal defects, exogenous PTHrP and PTH enhanced survival of the animals by improving serum calcium. Both proteins increased renal calcium transporter expression and long bone length and augmented growth plate chondrocyte proliferation, differentiation, and cartilage matrix mineralization. Cortical and trabecular bone mass was increased with augmented osteoblast number and activity; however, bone resorption was not increased.<\/jats:p>\n               <jats:p>Conclusions: PTHrP and PTH reduced hypocalcemia by enhancing renal calcium reabsorption but not by increasing bone resorption. The major skeletal effects of exogenous PTHrP and PTH were to increase bone anabolism.<\/jats:p>","DOI":"10.1359\/jbmr.050608","type":"journal-article","created":{"date-parts":[[2006,4,27]],"date-time":"2006-04-27T00:41:38Z","timestamp":1146098498000},"page":"1766-1777","source":"Crossref","is-referenced-by-count":34,"title":["Exogenous PTH-Related Protein and PTH Improve Mineral and Skeletal Status in 25-Hydroxyvitamin D-1\u03b1-Hydroxylase and PTH Double Knockout Mice"],"prefix":"10.1093","volume":"20","author":[{"given":"Yingben","family":"Xue","sequence":"first","affiliation":[{"name":"Calcium Research Laboratory, McGill University Health Centre and Department of Medicine, McGill University, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zengli","family":"Zhang","sequence":"additional","affiliation":[{"name":"Calcium Research Laboratory, McGill University Health Centre and Department of Medicine, McGill University, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew C","family":"Karaplis","sequence":"additional","affiliation":[{"name":"Lady Davis Research Institute, Sir Mortimer B. Davis-Jewish General Hospital and Department of Medicine McGill University, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey N","family":"Hendy","sequence":"additional","affiliation":[{"name":"Calcium Research Laboratory, McGill University Health Centre and Department of Medicine, McGill University, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Goltzman","sequence":"additional","affiliation":[{"name":"Calcium Research Laboratory, McGill University Health Centre and Department of Medicine, McGill University, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dengshun","family":"Miao","sequence":"additional","affiliation":[{"name":"Center for Bone and Stem Cell Research, Nanjing Medical University, Nanjing, Jiangsu, China"},{"name":"Calcium Research Laboratory, McGill University Health Centre and Department of Medicine, McGill University, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,12,4]]},"reference":[{"key":"2024013019255167100_bib1","doi-asserted-by":"crossref","first-page":"5048","DOI":"10.1073\/pnas.84.14.5048","article-title":"Parathyroid hormone-related protein purified from a human lung cancer cell line","volume":"84","author":"Moseley","year":"1987","journal-title":"Proc Natl Acad Sci USA"},{"key":"2024013019255167100_bib2","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1172\/JCI113275","article-title":"Parathyroid hormonelike protein from human renal carcinoma cells. 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