{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T10:56:52Z","timestamp":1789642612662,"version":"4.0.0"},"reference-count":43,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2015,3,1]],"date-time":"2015-03-01T00:00:00Z","timestamp":1425168000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2015,3,1]],"date-time":"2015-03-01T00:00:00Z","timestamp":1425168000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2015,1,10]],"date-time":"2015-01-10T00:00:00Z","timestamp":1420848000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003382","name":"Core Research for Evolutional Science and Technology","doi-asserted-by":"publisher","award":["13418291"],"award-info":[{"award-number":["13418291"]}],"id":[{"id":"10.13039\/501100003382","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["25253090"],"award-info":[{"award-number":["25253090"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Metabolism"],"published-print":{"date-parts":[[2015,3]]},"DOI":"10.1016\/j.molmet.2015.01.002","type":"journal-article","created":{"date-parts":[[2015,1,21]],"date-time":"2015-01-21T23:02:12Z","timestamp":1421881332000},"page":"175-185","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":15,"title":["Genetic determination of the cellular basis of the ghrelin-dependent bone remodeling"],"prefix":"10.1016","volume":"4","author":[{"given":"Chengshan","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Fukuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Ochi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoko","family":"Sunamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Okawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Takeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"2","key":"10.1016\/j.molmet.2015.01.002_bib1","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nm.3074","article-title":"WNT signaling in bone homeostasis and disease: from human mutations to treatments","volume":"19","author":"Baron","year":"2013","journal-title":"Nature Medicine"},{"issue":"8","key":"10.1016\/j.molmet.2015.01.002_bib2","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1038\/nrg1122","article-title":"Genetic regulation of osteoclast development and function","volume":"4","author":"Teitelbaum","year":"2003","journal-title":"Nature Reviews Genetics"},{"issue":"5","key":"10.1016\/j.molmet.2015.01.002_bib3","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.1210\/en.2012-1022","article-title":"Minireview: the link between fat and bone: does mass beget mass?","volume":"153","author":"Zaidi","year":"2012","journal-title":"Endocrinology"},{"issue":"5","key":"10.1016\/j.molmet.2015.01.002_bib4","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/j.bone.2008.01.005","article-title":"Molecular bases of the sympathetic regulation of bone mass","volume":"42","author":"Takeda","year":"2008","journal-title":"Bone"},{"issue":"2","key":"10.1016\/j.molmet.2015.01.002_bib5","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S0092-8674(00)81558-5","article-title":"Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass","volume":"100","author":"Ducy","year":"2000","journal-title":"Cell"},{"key":"10.1016\/j.molmet.2015.01.002_bib6","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1152\/physrev.00012.2004","article-title":"Ghrelin: structure and function","volume":"85","author":"Kojima","year":"2005","journal-title":"Physiological Reviews"},{"key":"10.1016\/j.molmet.2015.01.002_bib7","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1385\/ENDO:22:1:5","article-title":"Regulation of ghrelin secretion and action","volume":"22","author":"Camina","year":"2003","journal-title":"Endocrine"},{"issue":"12","key":"10.1016\/j.molmet.2015.01.002_bib8","doi-asserted-by":"crossref","first-page":"2086","DOI":"10.1007\/s11695-013-1016-x","article-title":"Effect of bariatric surgery on bone mineral density: comparison of gastric bypass and sleeve gastrectomy","volume":"23","author":"Vilarrasa","year":"2013","journal-title":"Obesity Surgery"},{"key":"10.1016\/j.molmet.2015.01.002_bib9","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1359\/JBMR.041237","article-title":"Ghrelin directly regulates bone formation","volume":"20","author":"Fukushima","year":"2005","journal-title":"Journal of Bone and Mineral Research"},{"key":"10.1016\/j.molmet.2015.01.002_bib10","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1007\/s12020-008-9117-3","article-title":"Ghrelin stimulates proliferation of human osteoblastic TE85 cells via NO\/cGMP signaling pathway","volume":"35","author":"Wang","year":"2009","journal-title":"Endocrine"},{"key":"10.1016\/j.molmet.2015.01.002_bib11","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1677\/joe.1.05837","article-title":"Ghrelin regulates proliferation and differentiation of osteoblastic cells","volume":"184","author":"Maccarinelli","year":"2005","journal-title":"Journal of Endocrinology"},{"key":"10.1016\/j.molmet.2015.01.002_bib12","doi-asserted-by":"crossref","first-page":"3593","DOI":"10.1210\/en.2012-1277","article-title":"An age-dependent interaction with leptin unmasks ghrelin's bone-protective effects","volume":"153","author":"van der Velde","year":"2012","journal-title":"Endocrinology"},{"key":"10.1016\/j.molmet.2015.01.002_bib13","doi-asserted-by":"crossref","first-page":"3564","DOI":"10.1172\/JCI26002","article-title":"Mice lacking ghrelin receptors resist the development of diet-induced obesity","volume":"115","author":"Zigman","year":"2005","journal-title":"Journal of Clinical Investigation"},{"issue":"16","key":"10.1016\/j.molmet.2015.01.002_bib14","doi-asserted-by":"crossref","first-page":"3231","DOI":"10.1242\/dev.02480","article-title":"Distinct roles for hedgehog and canonical Wnt signaling in specification, differentiation and maintenance of osteoblast progenitors","volume":"133","author":"Rodda","year":"2006","journal-title":"Development"},{"issue":"7","key":"10.1016\/j.molmet.2015.01.002_bib15","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1038\/nm1425","article-title":"Conditional ablation of Stat3 or Socs3 discloses a dual role for reactive astrocytes after spinal cord injury","volume":"12","author":"Okada","year":"2006","journal-title":"Nature Medicine"},{"issue":"5","key":"10.1016\/j.molmet.2015.01.002_bib16","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.cell.2007.07.025","article-title":"Estrogen prevents bone loss via estrogen receptor alpha and induction of Fas ligand in osteoclasts","volume":"130","author":"Nakamura","year":"2007","journal-title":"Cell"},{"issue":"7450","key":"10.1016\/j.molmet.2015.01.002_bib17","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1038\/nature12115","article-title":"Sema3A regulates bone-mass accrual through sensory innervations","volume":"497","author":"Fukuda","year":"2013","journal-title":"Nature"},{"issue":"8","key":"10.1016\/j.molmet.2015.01.002_bib18","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1002\/jbmr.406","article-title":"Central (ICV) leptin injection increases bone formation, bone mineral density, muscle mass, serum IGF-1, and the expression of osteogenic genes in leptin-deficient ob\/ob mice","volume":"26","author":"Bartell","year":"2011","journal-title":"Journal of Bone and Mineral Research"},{"key":"10.1016\/j.molmet.2015.01.002_bib19","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1038\/nm1640","article-title":"Central control of bone remodeling by neuromedin U","volume":"13","author":"Sato","year":"2007","journal-title":"Nature Medicine"},{"issue":"1","key":"10.1016\/j.molmet.2015.01.002_bib20","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.molmet.2013.10.001","article-title":"Arcuate AgRP neurons mediate orexigenic and glucoregulatory actions of ghrelin","volume":"3","author":"Wang","year":"2014","journal-title":"Molecular Metabolism"},{"key":"10.1016\/j.molmet.2015.01.002_bib21","doi-asserted-by":"crossref","first-page":"e44089","DOI":"10.1371\/journal.pone.0044089","article-title":"Hindbrain ghrelin receptor signaling is sufficient to maintain fasting glucose","volume":"7","author":"Scott","year":"2012","journal-title":"PloS One"},{"key":"10.1016\/j.molmet.2015.01.002_bib22","doi-asserted-by":"crossref","first-page":"2684","DOI":"10.1172\/JCI57660","article-title":"Ghrelin mediates stress-induced food-reward behavior in mice","volume":"121","author":"Chuang","year":"2011","journal-title":"Journal of Clinical Investigation"},{"issue":"6","key":"10.1016\/j.molmet.2015.01.002_bib23","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1083\/jcb.200207165","article-title":"Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1\/2 and PI 3-kinase\/AKT","volume":"159","author":"Baldanzi","year":"2002","journal-title":"Journal of Cell Biology"},{"issue":"1","key":"10.1016\/j.molmet.2015.01.002_bib24","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1002\/jcp.21109","article-title":"Stimulation by ghrelin of p42\/p44 mitogen-activated protein kinase through the GHS-R1a receptor: role of G-proteins and beta-arrestins","volume":"213","author":"Camina","year":"2007","journal-title":"Journal of Cellular Physiology"},{"issue":"9","key":"10.1016\/j.molmet.2015.01.002_bib25","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1210\/me.2011-1001","article-title":"Ghrelin directly stimulates glucagon secretion from pancreatic alpha-cells","volume":"25","author":"Chuang","year":"2011","journal-title":"Molecular Endocrinology"},{"issue":"4","key":"10.1016\/j.molmet.2015.01.002_bib26","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1084\/jem.20102608","article-title":"Genetic determination of the cellular basis of the sympathetic regulation of bone mass accrual","volume":"208","author":"Kajimura","year":"2011","journal-title":"Journal of Experimental Medicine"},{"issue":"1","key":"10.1016\/j.molmet.2015.01.002_bib27","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1172\/JCI59466","article-title":"Administration of BMP2\/7 in utero partially reverses Rubinstein-Taybi syndrome-like skeletal defects induced by Pdk1 or Cbp mutations in mice","volume":"122","author":"Shim","year":"2012","journal-title":"Journal of Clinical Investigation"},{"issue":"9","key":"10.1016\/j.molmet.2015.01.002_bib28","doi-asserted-by":"crossref","first-page":"3561","DOI":"10.1210\/en.2014-1126","article-title":"An early reduction in GH peak amplitude in preproghrelin-deficient male mice has a minor impact on linear growth","volume":"155","author":"Hassouna","year":"2014","journal-title":"Endocrinology"},{"issue":"12","key":"10.1016\/j.molmet.2015.01.002_bib29","doi-asserted-by":"crossref","first-page":"3573","DOI":"10.1172\/JCI26003","article-title":"Absence of ghrelin protects against early-onset obesity","volume":"115","author":"Wortley","year":"2005","journal-title":"Journal of Clinical Investigation"},{"key":"10.1016\/j.molmet.2015.01.002_bib30","doi-asserted-by":"crossref","first-page":"4679","DOI":"10.1073\/pnas.0305930101","article-title":"Ghrelin stimulation of growth hormone release and appetite is mediated through the growth hormone secretagogue receptor","volume":"101","author":"Sun","year":"2004","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"4","key":"10.1016\/j.molmet.2015.01.002_bib31","doi-asserted-by":"crossref","first-page":"301","DOI":"10.3109\/00365529309090245","article-title":"Gastrectomy causes bone loss in the rat: is lack of gastric acid responsible?","volume":"28","author":"Persson","year":"1993","journal-title":"Scandinavian Journal of Gastroenterology"},{"issue":"2","key":"10.1016\/j.molmet.2015.01.002_bib32","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s002230010025","article-title":"Osteoporosis after gastrectomy: bone mineral density of lumbar spine assessed by dual-energy X-ray absorptiometry","volume":"66","author":"Adachi","year":"2000","journal-title":"Calcified Tissue International"},{"issue":"7","key":"10.1016\/j.molmet.2015.01.002_bib33","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1381\/0960892054621125","article-title":"Sleeve gastrectomy and gastric banding: effects on plasma ghrelin levels","volume":"15","author":"Langer","year":"2005","journal-title":"Obesity Surgery"},{"issue":"5905","key":"10.1016\/j.molmet.2015.01.002_bib34","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1126\/science.1163971","article-title":"Regulation of pancreatic beta cell mass by neuronal signals from the liver","volume":"322","author":"Imai","year":"2008","journal-title":"Science"},{"issue":"4","key":"10.1016\/j.molmet.2015.01.002_bib35","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.nut.2012.07.017","article-title":"Probiotics: interaction with gut microbiome and antiobesity potential","volume":"29","author":"Arora","year":"2013","journal-title":"Nutrition"},{"issue":"6150","key":"10.1016\/j.molmet.2015.01.002_bib36","doi-asserted-by":"crossref","first-page":"1241214","DOI":"10.1126\/science.1241214","article-title":"Gut microbiota from twins discordant for obesity modulate metabolism in mice","volume":"341","author":"Ridaura","year":"2013","journal-title":"Science"},{"key":"10.1016\/j.molmet.2015.01.002_bib37","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1097\/MED.0b013e3283344a05","article-title":"Gastrointestinal peptides and bone health","volume":"17","author":"Wong","year":"2010","journal-title":"Current Opinion in Endocrinology, Diabetes, and Obesity"},{"issue":"5","key":"10.1016\/j.molmet.2015.01.002_bib38","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1016\/j.cell.2009.06.051","article-title":"A\u00a0serotonin-dependent mechanism explains the leptin regulation of bone mass, appetite, and energy expenditure","volume":"138","author":"Yadav","year":"2009","journal-title":"Cell"},{"issue":"1","key":"10.1016\/j.molmet.2015.01.002_bib39","doi-asserted-by":"crossref","first-page":"e85161","DOI":"10.1371\/journal.pone.0085161","article-title":"Osx-Cre targets multiple cell types besides osteoblast lineage in postnatal mice","volume":"9","author":"Chen","year":"2014","journal-title":"PloS One"},{"issue":"4","key":"10.1016\/j.molmet.2015.01.002_bib40","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/BF03021409","article-title":"Insulin-like growth factor-1 and growth hormone (GH) have distinct and overlapping anabolic effects in GH-deficient rats","volume":"3","author":"Clark","year":"1995","journal-title":"Endocrine"},{"issue":"9","key":"10.1016\/j.molmet.2015.01.002_bib41","first-page":"1131","article-title":"Ghrelin protects myocardium from isoproterenol-induced injury in rats","volume":"25","author":"Chang","year":"2004","journal-title":"Acta Pharmacologica Sinica"},{"issue":"2","key":"10.1016\/j.molmet.2015.01.002_bib42","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1530\/eje.0.1500173","article-title":"Expression of ghrelin and biological activity of specific receptors for ghrelin and des-acyl ghrelin in human prostate neoplasms and related cell lines","volume":"150","author":"Cassoni","year":"2004","journal-title":"European Journal of Endocrinology"},{"key":"10.1016\/j.molmet.2015.01.002_bib43","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1210\/jc.2012-4247","article-title":"Clinical review: the human experience with ghrelin administration","volume":"98","author":"Garin","year":"2013","journal-title":"Journal of Clinical Endocrinology & Metabolism"}],"container-title":["Molecular Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2212877815000034?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2212877815000034?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:14:54Z","timestamp":1761956094000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2212877815000034"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,3]]},"references-count":43,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2015,3]]}},"alternative-id":["S2212877815000034"],"URL":"https:\/\/doi.org\/10.1016\/j.molmet.2015.01.002","relation":{},"ISSN":["2212-8778"],"issn-type":[{"value":"2212-8778","type":"print"}],"subject":[],"published":{"date-parts":[[2015,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Genetic determination of the cellular basis of the ghrelin-dependent bone remodeling","name":"articletitle","label":"Article Title"},{"value":"Molecular Metabolism","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.molmet.2015.01.002","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2015 The Authors. Published by Elsevier GmbH","name":"copyright","label":"Copyright"}]}}