{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T06:05:20Z","timestamp":1783577120088,"version":"3.55.0"},"reference-count":64,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2024,4,13]],"date-time":"2024-04-13T00:00:00Z","timestamp":1712966400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81991511"],"award-info":[{"award-number":["81991511"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32300965"],"award-info":[{"award-number":["32300965"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82202654"],"award-info":[{"award-number":["82202654"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2023M731545"],"award-info":[{"award-number":["2023M731545"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hypercholesterolaemia is a systemic metabolic disease, but the role of organs other than liver in cholesterol metabolism is unappreciated. The phenotypic characterization of the <jats:italic>Tsc1<jats:sup>Dmp1<\/jats:sup><\/jats:italic> mice reveal that genetic depletion of tuberous sclerosis complex 1 (TSC1) in osteocytes\/osteoblasts (<jats:italic>Dmp1<\/jats:italic>\u2010<jats:italic>Cre<\/jats:italic>) triggers progressive increase in serum cholesterol level. The resulting cholesterol metabolic dysregulation is shown to be associated with upregulation and elevation of serum amyloid A3 (SAA3), a lipid metabolism related factor, in the bone and serum respectively. SAA3, elicited from the bone, bound to toll\u2010like receptor 4 (TLR4) on hepatocytes to phosphorylate c\u2010Jun, and caused impeded conversion of cholesterol to bile acids via suppression on <jats:italic>cholesterol 7 \u03b1\u2010hydroxylase<\/jats:italic> (<jats:italic>Cyp7a1<\/jats:italic>) expression. Ablation of <jats:italic>Saa3<\/jats:italic> in <jats:italic>Tsc1<jats:sup>Dmp1<\/jats:sup><\/jats:italic> mice prevented the CYP7A1 reduction in liver and cholesterol elevation in serum. These results expand the understanding of bone function and hepatic regulation of cholesterol metabolism and uncover a potential therapeutic use of pharmacological modulation of SAA3 in hypercholesterolaemia.<\/jats:p>","DOI":"10.1002\/advs.202307818","type":"journal-article","created":{"date-parts":[[2024,4,13]],"date-time":"2024-04-13T14:43:12Z","timestamp":1713019392000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Osteocytes\/Osteoblasts Produce SAA3 to Regulate Hepatic Metabolism of Cholesterol"],"prefix":"10.1002","volume":"11","author":[{"given":"Shijiang","family":"Huang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Organ Failure Research Department of Cell Biology School of Basic Medical Sciences Southern Medical University  Guangzhou Guangdong 510515 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanjun","family":"Jiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research Department of Cell Biology School of Basic Medical Sciences Southern Medical University  Guangzhou Guangdong 510515 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Nanfang Hospital Southern Medical University  Guangzhou Guangdong 510515 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linlin","family":"Mao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research Department of Cell Biology School of Basic Medical Sciences Southern Medical University  Guangzhou Guangdong 510515 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyou","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology School of Basic Medical Sciences Southern Medical University  Guangzhou Guangdong 510515 China"},{"name":"Equipment Material Department West China Xiamen Hospital of Sichuan University  Xiamen Fujian 361000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research Department of Cell Biology School of Basic Medical Sciences Southern Medical University  Guangzhou Guangdong 510515 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhui","family":"Jiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research Department of Cell Biology School of Basic Medical Sciences Southern Medical University  Guangzhou Guangdong 510515 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research Department of Cell Biology School of Basic Medical Sciences Southern Medical University  Guangzhou Guangdong 510515 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research Department of Cell Biology School of Basic Medical Sciences Southern Medical University  Guangzhou Guangdong 510515 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Xiong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research Department of Cell Biology School of Basic Medical Sciences Southern Medical University  Guangzhou Guangdong 510515 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wuju","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research Department of Cell Biology School of Basic Medical Sciences Southern Medical University  Guangzhou Guangdong 510515 China"},{"name":"Central Laboratory The Fifth Affiliated Hospital Southern Medical University  Guangzhou Guangdong 510900 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolin","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research Department of Cell Biology School of Basic Medical Sciences Southern Medical University  Guangzhou Guangdong 510515 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research Department of Cell Biology School of Basic Medical Sciences Southern Medical University  Guangzhou Guangdong 510515 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochun","family":"Bai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research Department of Cell Biology School of Basic Medical Sciences Southern Medical University  Guangzhou Guangdong 510515 China"},{"name":"Guangdong Provincial Key Laboratory of Bone and Joint Degenerative Diseases The Third Affiliated Hospital of Southern Medical University  Guangzhou Guangdong 510630 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Guo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research Department of Cell Biology School of Basic Medical Sciences Southern Medical University  Guangzhou Guangdong 510515 China"},{"name":"The Tenth Affiliated Hospital Southern Medical University  Dongguan Guangdong 523018 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,13]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1806939"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.02.019"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc.15.161"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.11.011"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.01.019"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2015.03.002"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2020.100861"},{"key":"e_1_2_9_5_3","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020007731"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2004.06.014"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2005.01.002"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-022-00665-x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1707876115"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.2174\/1872208311206030223"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-017-0049-4"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-018-0041-8"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-11-749838"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13885"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17363-6"},{"key":"e_1_2_9_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2018.12.021"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21183"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.08.042"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2019.04.008"},{"key":"e_1_2_9_18_2","doi-asserted-by":"publisher","DOI":"10.3390\/nu11112588"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2023.1197432"},{"key":"e_1_2_9_19_2","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-018-0047-0"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1993.1209"},{"key":"e_1_2_9_20_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1994.1052"},{"key":"e_1_2_9_20_3","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.3VMR0315-080R"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.1999.00657.x"},{"key":"e_1_2_9_21_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M080887"},{"key":"e_1_2_9_21_3","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-66898-7"},{"key":"e_1_2_9_21_4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0108564"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00774-004-0504-4"},{"key":"e_1_2_9_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/boneres.2016.49"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2760(90)90030-2"},{"key":"e_1_2_9_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tvjl.2005.04.021"},{"key":"e_1_2_9_23_3","doi-asserted-by":"publisher","DOI":"10.1292\/jvms.55.1011"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7163-3_16"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.251194298"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.05.047"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00039.2022"},{"key":"e_1_2_9_27_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01011.2018"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.26163"},{"key":"e_1_2_9_29_1","first-page":"6","volume":"91","author":"Zhang J.","year":"2017","journal-title":"J Virol."},{"key":"e_1_2_9_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.29850"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.163.4.2143"},{"key":"e_1_2_9_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(94)90166-X"},{"key":"e_1_2_9_30_3","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M005378200"},{"key":"e_1_2_9_30_4","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003-1261"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000130642.79868.B2"},{"key":"e_1_2_9_31_2","doi-asserted-by":"publisher","DOI":"10.1253\/circj.71.186"},{"key":"e_1_2_9_31_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2004.01.030"},{"key":"e_1_2_9_31_4","doi-asserted-by":"publisher","DOI":"10.1179\/135100009X12525712409490"},{"key":"e_1_2_9_31_5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200003233421202"},{"key":"e_1_2_9_31_6","doi-asserted-by":"publisher","DOI":"10.1111\/eci.13095"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2011.00186"},{"key":"e_1_2_9_32_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M054015"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOL.0000000000000616"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-008-8321-x"},{"key":"e_1_2_9_34_2","doi-asserted-by":"publisher","DOI":"10.1369\/jhc.2010.956821"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1717802115"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11883-006-0066-0"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1089\/dna.1991.10.651"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-41769-7_17"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202307818","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T20:53:17Z","timestamp":1759783997000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202307818"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,13]]},"references-count":64,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["10.1002\/advs.202307818"],"URL":"https:\/\/doi.org\/10.1002\/advs.202307818","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,13]]},"assertion":[{"value":"2023-10-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2307818"}}