{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T18:33:52Z","timestamp":1790102032159,"version":"4.0.1"},"reference-count":60,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:00:00Z","timestamp":1743120000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:00:00Z","timestamp":1743120000000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:00:00Z","timestamp":1743120000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2022R1A2C3006002"],"award-info":[{"award-number":["2022R1A2C3006002"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002631","name":"Gachon University","doi-asserted-by":"publisher","award":["FRD2023-12"],"award-info":[{"award-number":["FRD2023-12"]}],"id":[{"id":"10.13039\/501100002631","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2022R1F1A1074610"],"award-info":[{"award-number":["2022R1F1A1074610"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2022R1A4A1025913"],"award-info":[{"award-number":["2022R1A4A1025913"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2023-00217798"],"award-info":[{"award-number":["RS-2023-00217798"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2021R1A2C3003675"],"award-info":[{"award-number":["2021R1A2C3003675"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2022R1A2C1006105"],"award-info":[{"award-number":["2022R1A2C1006105"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002642","name":"Korea University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002642","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Osteoporosis, characterized by reduced bone density and strength, increases fracture risk, pain, and limits mobility. Established therapies of parathyroid hormone (PTH) analogs effectively promote bone formation and reduce fractures in severe osteoporosis, but their use is limited by potential adverse effects. In the pursuit of safer osteoporosis treatments, we investigated\n                    <jats:sup>R25C<\/jats:sup>\n                    PTH, a PTH variant wherein the native arginine at position 25 is substituted by cysteine. These studies were prompted by our finding of high bone mineral density in a hypoparathyroidism patient with the R25C homozygous mutation, and we explored its effects on PTH type-1 receptor (PTH1R) signaling in cells and bone metabolism in mice. Our findings indicate that\n                    <jats:sup>R25C<\/jats:sup>\n                    PTH(1\u201384) forms dimers both intracellularly and extracellularly, and the synthetic dimeric peptide,\n                    <jats:sup>R25C<\/jats:sup>\n                    PTH(1\u201334), exhibits altered activity in PTH1R-mediated cyclic AMP (cAMP) response. Upon a single injection in mice, dimeric\n                    <jats:sup>R25C<\/jats:sup>\n                    PTH(1\u201334) induced acute calcemic and phosphaturic responses comparable to PTH(1\u201334). Furthermore, repeated daily injections increased calvarial bone thickness in intact mice and improved trabecular and cortical bone parameters in ovariectomized (OVX) mice, akin to PTH(1\u201334). The overall results reveal a capacity of a dimeric PTH peptide ligand to activate the PTH1R in vitro and in vivo as PTH, suggesting a potential path of therapeutic PTH analog development.\n                  <\/jats:p>","DOI":"10.7554\/elife.97579","type":"journal-article","created":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T09:25:22Z","timestamp":1719307522000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.97579","source":"Crossref","is-referenced-by-count":4,"title":["Dimeric R25CPTH(1\u201334) activates the parathyroid hormone-1 receptor in vitro and stimulates bone formation in osteoporotic female mice"],"prefix":"10.7554","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1239-3783","authenticated-orcid":true,"given":"Minsoo","family":"Noh","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03ryywt80","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Internal Medicine and Laboratory of Genomics and Translational Medicine, Gachon University College of Medicine","place":["Incheon, Republic of Korea"]},{"id":[{"id":"https:\/\/ror.org\/047dqcg40","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Life Sciences, Korea University","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Xiangguo","family":"Che","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/040c17130","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University","place":["Daegu, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Xian","family":"Jin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/040c17130","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University","place":["Daegu, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Dong-Kyo","family":"Lee","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/040c17130","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University","place":["Daegu, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"given":"Hyun-Ju","family":"Kim","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/040c17130","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University","place":["Daegu, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Doo Ri","family":"Park","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/053fp5c05","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Life Sciences, Multitasking Macrophage Research Center, Ewha Womans University","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"given":"Soo Young","family":"Lee","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/053fp5c05","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Life Sciences, Multitasking Macrophage Research Center, Ewha Womans University","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Hunsang","family":"Lee","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/047dqcg40","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Life Sciences, Korea University","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Thomas J","family":"Gardella","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/002pd6e78","id-type":"ROR","asserted-by":"publisher"}],"name":"Endocrine Unit, Massachusetts General Hospital and Harvard Medical School","place":["Boston, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Je-Yong","family":"Choi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/040c17130","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University","place":["Daegu, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"corresponding-author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9444-5849","authenticated-orcid":true,"given":"Sihoon","family":"Lee","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03ryywt80","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Internal Medicine and Laboratory of Genomics and Translational Medicine, Gachon University College of Medicine","place":["Incheon, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"corresponding-author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"4374","published-online":{"date-parts":[[2025,3,28]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"2732","DOI":"10.1073\/pnas.89.7.2732","type":"journal-article","article-title":"Expression cloning of a common receptor for parathyroid hormone and parathyroid hormone-related peptide from rat osteoblast-like cells: a single receptor stimulates intracellular accumulation of both cAMP and inositol trisphosphates and increases intracellular free calcium","volume":"89","author":"Abou-Samra","year":"1992","journal-title":"PNAS"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1515\/jpem-2021-0752","type":"journal-article","article-title":"Homozygous missense variant of PTH","volume":"35","author":"Andersen","year":"2022","journal-title":"Journal of Pediatric Endocrinology & Metabolism: JPEM"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1007\/s12020-016-0888-7","type":"journal-article","article-title":"From disease to treatment: from rare skeletal disorders to treatments for osteoporosis","volume":"52","author":"Appelman-Dijkstra","year":"2016","journal-title":"Endocrine"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1172\/JCI114811","type":"journal-article","article-title":"Mutation of the signal peptide-encoding region of the preproparathyroid hormone gene in familial isolated hypoparathyroidism","volume":"86","author":"Arnold","year":"1990","journal-title":"The Journal of Clinical Investigation"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"3700","DOI":"10.1210\/jc.2016-1640","type":"journal-article","article-title":"A novel human PTH analog [Cys25]hPTH(1\u201334) restores bone mass in ovariectomized mice","volume":"101","author":"Bae","year":"2016","journal-title":"The Journal of Clinical Endocrinology & Metabolism"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"25970","DOI":"10.1074\/jbc.M103109200","type":"journal-article","article-title":"Dimerization of resistin and resistin-like molecules is determined by a single cysteine","volume":"276","author":"Banerjee","year":"2001","journal-title":"The Journal of Biological Chemistry"},{"key":"bib7","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1093\/clinchem\/48.10.1731","type":"journal-article","article-title":"Kinetic analyses of parathyroid hormone clearance as measured by three rapid immunoassays during parathyroidectomy","volume":"48","author":"Bieglmayer","year":"2002","journal-title":"Clinical Chemistry"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"1189","DOI":"10.1056\/NEJMoa030897","type":"journal-article","article-title":"Ten years\u2019 experience with alendronate for osteoporosis in postmenopausal women","volume":"350","author":"Bone","year":"2004","journal-title":"The New England Journal of Medicine"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.1002\/jbmr.141","type":"journal-article","article-title":"Guidelines for assessment of bone microstructure in rodents using micro-computed tomography","volume":"25","author":"Bouxsein","year":"2010","journal-title":"Journal of Bone and Mineral Research"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1038\/nrendo.2015.139","type":"journal-article","article-title":"PTH receptor-1 signalling-mechanistic insights and therapeutic prospects","volume":"11","author":"Cheloha","year":"2015","journal-title":"Nature Reviews. Endocrinology"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"F1005","DOI":"10.1152\/ajprenal.00013.2004","type":"journal-article","article-title":"Role of the calcium-sensing receptor in parathyroid gland physiology","volume":"286","author":"Chen","year":"2004","journal-title":"American Journal of Physiology. Renal Physiology"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1038\/s41589-020-0567-0","type":"journal-article","article-title":"Allosteric interactions in the parathyroid hormone GPCR-arrestin complex formation","volume":"16","author":"Clark","year":"2020","journal-title":"Nature Chemical Biology"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"1532","DOI":"10.1056\/NEJMoa1607948","type":"journal-article","article-title":"Romosozumab treatment in postmenopausal women with osteoporosis","volume":"375","author":"Cosman","year":"2016","journal-title":"The New England Journal of Medicine"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1210\/me.2007-0274","type":"journal-article","article-title":"Altered selectivity of parathyroid hormone (PTH) and PTH-related protein (PTHrP) for distinct conformations of the PTH\/PTHrP receptor","volume":"22","author":"Dean","year":"2008","journal-title":"Molecular Endocrinology"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1002\/jbmr.1805","type":"journal-article","article-title":"Standardized nomenclature, symbols, and units for bone histomorphometry: a 2012 update of the report of the ASBMR Histomorphometry Nomenclature Committee","volume":"28","author":"Dempster","year":"2013","journal-title":"Journal of Bone and Mineral Research"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"F223","DOI":"10.1152\/ajprenal.1990.258.2.F223","type":"journal-article","article-title":"PTH receptor coupling to phospholipase C is an alternate pathway of signal transduction in bone and kidney","volume":"258","author":"Dunlay","year":"1990","journal-title":"The American Journal of Physiology"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1016\/j.bone.2012.06.009","type":"journal-article","article-title":"A novel homozygous mutation in the parathyroid hormone gene (PTH) in A girl with isolated hypoparathyroidism","volume":"51","author":"Ertl","year":"2012","journal-title":"Bone"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1038\/nchembio.545","type":"journal-article","article-title":"Retromer terminates the generation of cAMP by internalized PTH receptors","volume":"7","author":"Feinstein","year":"2011","journal-title":"Nature Chemical Biology"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1023\/a:1026522619828","type":"journal-article","article-title":"Interaction of PTH and PTHrP with their receptors","volume":"1","author":"Gardella","year":"2000","journal-title":"Reviews in Endocrine & Metabolic Disorders"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1152\/physrev.1984.64.3.985","type":"journal-article","article-title":"Parathyroid hormone: biochemical aspects of biosynthesis, secretion, action, and metabolism","volume":"64","author":"Habener","year":"1984","journal-title":"Physiological Reviews"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"7741","DOI":"10.1074\/jbc.M009395200","type":"journal-article","article-title":"Evaluating the signal transduction mechanism of the parathyroid hormone 1 receptor: effect of receptor-G-protein interaction on the ligand binding mechanism and receptor conformation","volume":"276","author":"Hoare","year":"2001","journal-title":"The Journal of Biological Chemistry"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"6882","DOI":"10.1074\/jbc.272.11.6882","type":"journal-article","article-title":"Mutations in the second cytoplasmic loop of the rat parathyroid hormone (PTH)\/PTH-related protein receptor result in selective loss of PTH-stimulated phospholipase C activity","volume":"272","author":"Iida-Klein","year":"1997","journal-title":"The Journal of Biological Chemistry"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"1434","DOI":"10.1016\/j.bone.2007.03.017","type":"journal-article","article-title":"Molecular and cellular mechanisms of the anabolic effect of intermittent PTH","volume":"40","author":"Jilka","year":"2007","journal-title":"Bone"},{"key":"bib24","doi-asserted-by":"publisher","DOI":"10.1016\/j.jff.2024.106148","type":"journal-article","article-title":"Silk sericin-based functional food for osteoporosis prevention and therapy","volume":"116","author":"Jin","year":"2024","journal-title":"Journal of Functional Foods"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1126\/science.1658941","type":"journal-article","article-title":"A G protein-linked receptor for parathyroid hormone and parathyroid hormone-related peptide","volume":"254","author":"J\u00fcppner","year":"1991","journal-title":"Science"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"3731","DOI":"10.1073\/pnas.71.9.3731","type":"journal-article","article-title":"Pre-proparathyroid hormone: a direct translation product of parathyroid messenger RNA","volume":"71","author":"Kemper","year":"1974","journal-title":"PNAS"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1016\/S2213-8587(17)30188-2","type":"journal-article","article-title":"Osteoporosis treatment: recent developments and ongoing challenges","volume":"5","author":"Khosla","year":"2017","journal-title":"The Lancet. Diabetes & Endocrinology"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1038\/labinvest.2008.114","type":"journal-article","article-title":"Recent advances in the renal-skeletal-gut axis that controls phosphate homeostasis","volume":"89","author":"Kiela","year":"2009","journal-title":"Laboratory Investigation; a Journal of Technical Methods and Pathology"},{"key":"bib29","doi-asserted-by":"publisher","DOI":"10.1038\/srep22533","type":"journal-article","article-title":"Small molecule inhibited parathyroid hormone mediated cAMP response by N-terminal peptide binding","volume":"6","author":"Kumar","year":"2016","journal-title":"Scientific Reports"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"1803","DOI":"10.1002\/jbmr.2532","type":"journal-article","article-title":"A homozygous [Cys25]PTH(1-84) mutation that impairs PTH\/PTHrP receptor activation defines a novel form of hypoparathyroidism","volume":"30","author":"Lee","year":"2015","journal-title":"Journal of Bone and Mineral Research"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1002\/jbmr.2397","type":"journal-article","article-title":"Core binding factor \u03b2 of osteoblasts maintains cortical bone mass via stabilization of Runx2 in mice","volume":"30","author":"Lim","year":"2015","journal-title":"Journal of Bone and Mineral Research"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"5864","DOI":"10.1073\/pnas.1301674110","type":"journal-article","article-title":"Critical role of parathyroid hormone (PTH) receptor-1 phosphorylation in regulating acute responses to PTH","volume":"110","author":"Maeda","year":"2013","journal-title":"PNAS"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"3852","DOI":"10.1210\/jcem.83.11.5254","type":"journal-article","article-title":"Parathyroid hormone after adenectomy for primary hyperparathyroidism: a study of peptide hormone elimination kinetics in humans","volume":"83","author":"Maier","year":"1998","journal-title":"The Journal of Clinical Endocrinology and Metabolism"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1210\/endrev\/bnab005","type":"journal-article","article-title":"Physiological and pharmacological roles of PTH and PTHrP in bone using their shared receptor, PTH1R","volume":"42","author":"Martin","year":"2021","journal-title":"Endocrine Reviews"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1056\/NEJMoa1305224","type":"journal-article","article-title":"Romosozumab in postmenopausal women with low bone mineral density","volume":"370","author":"McClung","year":"2014","journal-title":"The New England Journal of Medicine"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"5253","DOI":"10.1074\/jbc.273.9.5253","type":"journal-article","article-title":"RNA-Protein binding and post-transcriptional regulation of parathyroid hormone gene expression by calcium and phosphate","volume":"273","author":"Moallem","year":"1998","journal-title":"The Journal of Biological Chemistry"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"16525","DOI":"10.1073\/pnas.0808750105","type":"journal-article","article-title":"Prolonged signaling at the parathyroid hormone receptor by peptide ligands targeted to a specific receptor conformation","volume":"105","author":"Okazaki","year":"2008","journal-title":"PNAS"},{"key":"bib38","first-page":"8","type":"journal-article","article-title":"Markers of bone turnover: biochemical and clinical perspectives","volume":"28","author":"Pagani","year":"2005","journal-title":"Journal of Endocrinological Investigation"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1002\/jbmr.1479","type":"journal-article","article-title":"Five years of denosumab exposure in women with postmenopausal osteoporosis: results from the first two years of the FREEDOM extension","volume":"27","author":"Papapoulos","year":"2012","journal-title":"Journal of Bone and Mineral Research"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1038\/ng0592-149","type":"journal-article","article-title":"A donor splice site mutation in the parathyroid hormone gene is associated with autosomal recessive hypoparathyroidism","volume":"1","author":"Parkinson","year":"1992","journal-title":"Nature Genetics"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"28382","DOI":"10.1074\/jbc.M109.022905","type":"journal-article","article-title":"Structural basis for parathyroid hormone-related protein binding to the parathyroid hormone receptor and design of conformation-selective peptides","volume":"284","author":"Pioszak","year":"2009","journal-title":"The Journal of Biological Chemistry"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1016\/S0140-6736(09)60250-6","type":"journal-article","article-title":"Zoledronic acid and risedronate in the prevention and treatment of glucocorticoid-induced osteoporosis (HORIZON): a multicentre, double-blind, double-dummy, randomised controlled trial","volume":"373","author":"Reid","year":"2009","journal-title":"Lancet"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1007\/pl00005830","type":"journal-article","article-title":"Serum CTX: a new marker of bone resorption that shows treatment effect more often than other markers because of low coefficient of variability and large changes with bisphosphonate therapy","volume":"66","author":"Rosen","year":"2000","journal-title":"Calcified Tissue International"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"2742","DOI":"10.1210\/jc.2015-4135","type":"journal-article","article-title":"Therapy of hypoparathyroidism with PTH(1-84): a prospective six year investigation of efficacy and safety","volume":"101","author":"Rubin","year":"2016","journal-title":"The Journal of Clinical Endocrinology and Metabolism"},{"key":"bib45","doi-asserted-by":"publisher","DOI":"10.1186\/s13018-021-02772-0","type":"journal-article","article-title":"The global prevalence of osteoporosis in the world: a comprehensive systematic review and meta-analysis","volume":"16","author":"Salari","year":"2021","journal-title":"Journal of Orthopaedic Surgery and Research"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"4270","DOI":"10.1073\/pnas.82.12.4270","type":"journal-article","article-title":"Regulation by vitamin D metabolites of messenger ribonucleic acid for preproparathyroid hormone in isolated bovine parathyroid cells","volume":"82","author":"Silver","year":"1985","journal-title":"PNAS"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"46","DOI":"10.5152\/eurjrheum.2016.048","type":"journal-article","article-title":"An overview and management of osteoporosis","volume":"4","author":"S\u00f6zen","year":"2017","journal-title":"European Journal of Rheumatology"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"3792","DOI":"10.1210\/jcem.84.10.6070","type":"journal-article","article-title":"A novel mutation of the signal peptide of the preproparathyroid hormone gene associated with autosomal recessive familial isolated hypoparathyroidism","volume":"84","author":"Sunthornthepvarakul","year":"1999","journal-title":"The Journal of Clinical Endocrinology and Metabolism"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"614","DOI":"10.2174\/138920309789630534","type":"journal-article","article-title":"The role of thiols and disulfides on protein stability","volume":"10","author":"Trivedi","year":"2009","journal-title":"Current Protein & Peptide Science"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1080\/01926230252929882","type":"journal-article","article-title":"Skeletal changes in rats given daily subcutaneous injections of recombinant human parathyroid hormone (1-34) for 2 years and relevance to human safety","volume":"30","author":"Vahle","year":"2002","journal-title":"Toxicologic Pathology"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"2127","DOI":"10.1073\/pnas.80.8.2127","type":"journal-article","article-title":"Nucleotide sequence of the human parathyroid hormone gene","volume":"80","author":"Vasicek","year":"1983","journal-title":"PNAS"},{"key":"bib52","doi-asserted-by":"publisher","DOI":"10.1038\/boneres.2016.41","type":"journal-article","article-title":"Vitamin D, calcium homeostasis and aging","volume":"4","author":"Veldurthy","year":"2016","journal-title":"Bone Research"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1210\/edrv.22.5.0439","type":"journal-article","article-title":"Endocrine manifestations of stimulatory G protein alpha-subunit mutations and the role of genomic imprinting","volume":"22","author":"Weinstein","year":"2001","journal-title":"Endocrine Reviews"},{"key":"bib54","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-11-201","type":"journal-article","article-title":"The clinical utility of bone marker measurements in osteoporosis","volume":"11","author":"Wheater","year":"2013","journal-title":"Journal of Translational Medicine"},{"key":"bib55","doi-asserted-by":"publisher","first-page":"3294","DOI":"10.1073\/pnas.1814670116","type":"journal-article","article-title":"Ca(2+) allostery in PTH-receptor signaling","volume":"116","author":"White","year":"2019","journal-title":"PNAS"},{"key":"bib56","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1001\/jama.1996.03540080053029","type":"journal-article","article-title":"Synthetic human parathyroid hormone 1-34 vs calcitriol and calcium in the treatment of hypoparathyroidism","volume":"276","author":"Winer","year":"1996","journal-title":"JAMA"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/j.jpeds.2018.08.010","type":"journal-article","article-title":"Long-term parathyroid hormone 1-34 replacement therapy in children with hypoparathyroidism","volume":"203","author":"Winer","year":"2018","journal-title":"The Journal of Pediatrics"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1210\/mend-3-2-240","type":"journal-article","article-title":"Mutations in signal sequence cleavage domain of preproparathyroid hormone alter protein translocation, signal sequence cleavage, and membrane-binding properties","volume":"3","author":"Wiren","year":"1989","journal-title":"Molecular Endocrinology"},{"key":"bib59","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-34009-x","type":"journal-article","article-title":"Molecular insights into the distinct signaling duration for the peptide-induced PTH1R activation","volume":"13","author":"Zhai","year":"2022","journal-title":"Nature Communications"},{"key":"bib60","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1126\/science.aav7942","type":"journal-article","article-title":"Structure and dynamics of the active human parathyroid hormone receptor-1","volume":"364","author":"Zhao","year":"2019","journal-title":"Science"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/97579\/elife-97579-v1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/97579\/elife-97579-v1.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/97579","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:50:17Z","timestamp":1787565017000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/97579"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,28]]},"references-count":60,"alternative-id":["10.7554\/eLife.97579"],"URL":"https:\/\/doi.org\/10.7554\/elife.97579","archive":["CLOCKSS"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.03.13.584815","asserted-by":"subject"},{"id-type":"doi","id":"10.1101\/2024.03.13.584815","asserted-by":"object"}],"is-same-as":[{"id-type":"doi","id":"10.7554\/eLife.97579.5","asserted-by":"subject"}],"is-version-of":[{"id-type":"doi","id":"10.7554\/eLife.97579.1","asserted-by":"subject"},{"id-type":"doi","id":"10.7554\/eLife.97579.2","asserted-by":"subject"},{"id-type":"doi","id":"10.7554\/eLife.97579.3","asserted-by":"subject"},{"id-type":"doi","id":"10.7554\/eLife.97579.4","asserted-by":"subject"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,28]]},"assertion":[{"value":"single anonymised","name":"peer_review_transparency","label":"Peer review transparency","group":{"name":"peer_review_taxonomy"}},{"value":"other reviewer(s), editor","name":"peer_review_interaction","label":"Peer review interaction","group":{"name":"peer_review_taxonomy"}},{"value":"review summaries, review reports, author\/editor communication, reviewer identities reviewer opt in, editor identities","name":"peer_review_published","label":"Peer review published","group":{"name":"peer_review_taxonomy"}},{"value":"open (sign in with ORCID iD required)","name":"post_publication_commenting","label":"Post publication commenting","group":{"name":"post_publication_commenting"}}],"article-number":"RP97579"}}