{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:22:26Z","timestamp":1792801346641,"version":"4.5.0"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,3,9]],"date-time":"2018-03-09T00:00:00Z","timestamp":1520553600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81570953"],"award-info":[{"award-number":["81570953"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81500822"],"award-info":[{"award-number":["81500822"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the Project for Culturing Leading Talents in Scientific and Technological Innovation of Beijing","award":["Z171100001117169"],"award-info":[{"award-number":["Z171100001117169"]}]},{"name":"the PKU School of Stomatology for Talented Young Investigators","award":["PKUSS20140109"],"award-info":[{"award-number":["PKUSS20140109"]}]},{"name":"the Construction Program for National Key Clinical Specialty from National Health and Family Planning Commission of China","award":["2011"],"award-info":[{"award-number":["2011"]}],"id":[{"id":"https:\/\/ror.org\/052eegr76","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Stem Cell Res Ther"],"published-print":{"date-parts":[[2018,12]]},"DOI":"10.1186\/s13287-018-0809-1","type":"journal-article","created":{"date-parts":[[2018,3,9]],"date-time":"2018-03-09T08:43:54Z","timestamp":1520585034000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["LRRC15 promotes osteogenic differentiation of mesenchymal stem cells by modulating p65 cytoplasmic\/nuclear translocation"],"prefix":"10.1186","volume":"9","author":[{"given":"Yuejun","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunsong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longwei","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8651-2100","authenticated-orcid":false,"given":"Ping","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongsheng","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,3,9]]},"reference":[{"key":"809_CR1","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/j.stem.2008.03.002","volume":"2","author":"P Bianco","year":"2008","unstructured":"Bianco P, Robey P, Simmons P. Mesenchymal stem cells: revisiting history, concepts, and assays. Cell Stem Cell. 2008;2:313\u20139.","journal-title":"Cell Stem Cell."},{"key":"809_CR2","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1002\/stem.612","volume":"29","author":"B Levi","year":"2011","unstructured":"Levi B, Longaker M. Concise review: adipose-derived stromal cells for skeletal regenerative medicine. Stem Cells. 2011;29:576\u201382.","journal-title":"Stem Cells."},{"key":"809_CR3","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1038\/nm.3028","volume":"19","author":"P Bianco","year":"2013","unstructured":"Bianco P, Cao X, Frenette PS, Mao JJ, Robey PG, Simmons PJ, et al. The meaning, the sense and the significance: translating the science of mesenchymal stem cells into medicine. Nat Med. 2013;19:35\u201342.","journal-title":"Nat Med."},{"key":"809_CR4","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1089\/ten.teb.2008.0423","volume":"15","author":"T Rada","year":"2009","unstructured":"Rada T, Reis RL, Gomes ME. Adipose tissue-derived stem cells and their application in bone and cartilage tissue engineering. Tissue Eng Part B Rev. 2009;15:113\u201325.","journal-title":"Tissue Eng Part B Rev."},{"key":"809_CR5","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1016\/j.stem.2010.10.004","volume":"7","author":"S Teitelbaum","year":"2010","unstructured":"Teitelbaum S. Stem cells and osteoporosis therapy. Cell Stem Cell. 2010;7:553\u20134.","journal-title":"Cell Stem Cell."},{"key":"809_CR6","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1016\/j.it.2008.07.003","volume":"29","author":"SC Sun","year":"2008","unstructured":"Sun SC, Ley SC. New insights into NF-kappaB regulation and function. Trends Immunol. 2008;29:469\u201378.","journal-title":"Trends Immunol."},{"key":"809_CR7","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1038\/nrrheum.2010.133","volume":"6","author":"SA Krum","year":"2010","unstructured":"Krum SA, Chang J, Miranda-Carboni G, Wang CY. Novel functions for NFkappaB: inhibition of bone formation. Nat Rev Rheumatol. 2010;6:607\u201311.","journal-title":"Nat Rev Rheumatol."},{"key":"809_CR8","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1146\/annurev.immunol.16.1.225","volume":"16","author":"S Ghosh","year":"1998","unstructured":"Ghosh S, May MJ, Kopp EB. NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. Annu Rev Immunol. 1998;16:225\u201360.","journal-title":"Annu Rev Immunol."},{"key":"809_CR9","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1038\/sj.cdd.4401838","volume":"13","author":"N Perkins","year":"2006","unstructured":"Perkins N, Gilmore T. Good cop, bad cop: the different faces of NF-kappaB. Cell Death Differ. 2006;13:759\u201372.","journal-title":"Cell Death Differ."},{"key":"809_CR10","doi-asserted-by":"publisher","first-page":"2321","DOI":"10.1101\/gad.909001","volume":"15","author":"N Silverman","year":"2017","unstructured":"Silverman N, Maniatis T. NF-kappaB signaling pathways in mammalian and insect innate immunity. Genes Dev. 2017;15:2321\u201342.","journal-title":"Genes Dev."},{"key":"809_CR11","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1007\/s00441-013-1604-z","volume":"352","author":"Y Wang","year":"2013","unstructured":"Wang Y, Yan M, Yu Y, Wu J, Yu J, Fan Z. Estrogen deficiency inhibits the odonto\/osteogenic differentiation of dental pulp stem cells via activation of the NF-kappaB pathway. Cell Tissue Res. 2013;352:551\u20139.","journal-title":"Cell Tissue Res."},{"key":"809_CR12","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1038\/nm.1954","volume":"15","author":"J Chang","year":"2009","unstructured":"Chang J, Wang Z, Tang E, Fan Z, McCauley L, Franceschi R, et al. Inhibition of osteoblastic bone formation by nuclear factor-kappaB. Nat Med. 2009;15:682\u20139.","journal-title":"Nat Med."},{"key":"809_CR13","doi-asserted-by":"publisher","first-page":"1290","DOI":"10.1359\/jbmr.1998.13.8.1290","volume":"13","author":"K Kurokouchi","year":"1998","unstructured":"Kurokouchi K, Kambe F, Yasukawa K, Izumi R, Ishiguro N, Iwata H, et al. TNF-alpha increases expression of IL-6 and ICAM-1 genes through activation of NF-kappaB in osteoblast-like ROS17\/2.8 cells. J Bone Miner Res. 1998;13:1290\u20139.","journal-title":"J Bone Miner Res."},{"key":"809_CR14","doi-asserted-by":"publisher","first-page":"1525","DOI":"10.1172\/JCI22513","volume":"116","author":"K Aoki","year":"2006","unstructured":"Aoki K, Saito H, Itzstein C, Ishiguro M, Shibata T, Blanque R, et al. A TNF receptor loop peptide mimic blocks RANK ligand-induced signaling, bone resorption, and bone loss. J Clin Invest. 2006;116:1525\u201334.","journal-title":"J Clin Invest."},{"key":"809_CR15","doi-asserted-by":"publisher","first-page":"5562","DOI":"10.1074\/jbc.M112.426080","volume":"288","author":"Y Furuya","year":"2013","unstructured":"Furuya Y, Inagaki A, Khan M, Mori K, Penninger J, Nakamura M, et al. Stimulation of bone formation in cortical bone of mice treated with a receptor activator of nuclear factor-kappaB ligand (RANKL)-binding peptide that possesses osteoclastogenesis inhibitory activity. J Biol Chem. 2013;288:5562\u201371.","journal-title":"J Biol Chem."},{"key":"809_CR16","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1007\/s11154-014-9308-6","volume":"16","author":"T Martin","year":"2015","unstructured":"Martin T, Sims N. RANKL\/OPG: critical role in bone physiology. Rev Endocr Metab Disord. 2015;16:131\u20139.","journal-title":"Rev Endocr Metab Disord."},{"key":"809_CR17","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1359\/jbmr.070121","volume":"22","author":"Y Li","year":"2007","unstructured":"Li Y, Li A, Strait K, Zhang H, Nanes MS, Weitzmann MN. Endogenous TNFalpha lowers maximum peak bone mass and inhibits osteoblastic Smad activation through NF-kappaB. J Bone Miner Res. 2007;22:646\u201355.","journal-title":"J Bone Miner Res."},{"key":"809_CR18","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1016\/0968-0004(94)90090-6","volume":"19","author":"B Kobe","year":"1994","unstructured":"Kobe B, Deisenhofer J. The leucine-rich repeat: a versatile binding motif. Trends Biochem Sci. 1994;19:415\u201321.","journal-title":"Trends Biochem Sci."},{"key":"809_CR19","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1016\/S0959-440X(01)00266-4","volume":"11","author":"B Kobe","year":"2001","unstructured":"Kobe B, Kajava A. The leucine-rich repeat as a protein recognition motif. Curr Opin Struct Biol. 2001;11:725\u201332.","journal-title":"Curr Opin Struct Biol."},{"key":"809_CR20","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1177\/0022034511405389","volume":"23","author":"PR Cooper","year":"2011","unstructured":"Cooper PR, McLachlan JL, Simon S, Graham LW, Smith AJ. Mediators of inflammation and regeneration. Adv Dent Res. 2011;23:290\u20135.","journal-title":"Adv Dent Res."},{"key":"809_CR21","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1006\/bbrc.2001.6272","volume":"290","author":"K Satoh","year":"2002","unstructured":"Satoh K, Hata M, Yokot H. A novel member of the leucine-rich repeat superfamily induced in rat astrocytes by beta-amyloid. Biochem Biophys Res Commun. 2002;290:756\u201362.","journal-title":"Biochem Biophys Res Commun."},{"key":"809_CR22","doi-asserted-by":"publisher","first-page":"2332","DOI":"10.1002\/stem.2424","volume":"34","author":"P Zhang","year":"2016","unstructured":"Zhang P, Liu Y, Jin C, Zhang M, Lv L, Zhang X, et al. Histone H3K9 acetyltransferase PCAF is essential for osteogenic differentiation through bone morphogenetic protein signaling and may be involved in osteoporosis. Stem Cells. 2016;34:2332\u201341.","journal-title":"Stem Cells."},{"key":"809_CR23","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1002\/jbmr.2704","volume":"31","author":"P Zhang","year":"2016","unstructured":"Zhang P, Liu Y, Jin C, Zhang M, Tang F, Zhou Y. Histone acetyltransferase GCN5 regulates osteogenic differentiation of mesenchymal stem cells by inhibiting NF-kappaB. J Bone Miner Res. 2016;31:391\u2013402.","journal-title":"J Bone Miner Res."},{"key":"809_CR24","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1016\/j.stemcr.2017.01.028","volume":"8","author":"S Chen","year":"2017","unstructured":"Chen S, Zheng Y, Zhang S, Jia L, Zhou Y. Promotion effects of miR-375 on the osteogenic differentiation of human adipose-derived mesenchymal stem cells. Stem Cell Reports. 2017;8:773\u201386.","journal-title":"Stem Cell Reports."},{"key":"809_CR25","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.1002\/jbmr.141","volume":"25","author":"ML Bouxsein","year":"2010","unstructured":"Bouxsein ML, Boyd SK, Christiansen BA, Guldberg RE, Jepsen KJ, Muller R. Guidelines for assessment of bone microstructure in rodents using micro-computed tomography. J Bone Miner Res. 2010;25:1468\u201386.","journal-title":"J Bone Miner Res."},{"key":"809_CR26","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1172\/JCI33612","volume":"118","author":"S Khosla","year":"2008","unstructured":"Khosla S, Westendorf JJ, Oursler MJ. Building bone to reverse osteoporosis and repair fractures. J Clin Invest. 2008;118:421\u20138.","journal-title":"J Clin Invest."},{"key":"809_CR27","doi-asserted-by":"publisher","first-page":"1186","DOI":"10.1172\/JCI28550","volume":"116","author":"MN Weitzmann","year":"2006","unstructured":"Weitzmann MN, Pacifici R. Estrogen deficiency and bone loss: an inflammatory tale. J Clin Invest. 2006;116:1186\u201394.","journal-title":"J Clin Invest."},{"key":"809_CR28","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1111\/j.1749-6632.2009.05315.x","volume":"1192","author":"BF Boyce","year":"2010","unstructured":"Boyce BF, Yao Z, Xing L. Functions of nuclear factor \u03baB in bone. Ann N Y Acad Sci. 2010;1192:367\u201375.","journal-title":"Ann N Y Acad Sci."},{"key":"809_CR29","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1111\/j.0105-2896.2005.00329.x","volume":"208","author":"E Jimi","year":"2005","unstructured":"Jimi E, Ghosh S. Role of nuclear factor-\u03baB in the immune system and bone. Immunol Rev. 2005;208:80\u20137.","journal-title":"Immunol Rev."},{"key":"809_CR30","doi-asserted-by":"publisher","first-page":"2030","DOI":"10.1210\/me.2010-0189","volume":"24","author":"M Almeida","year":"2010","unstructured":"Almeida M, Han L, Ambrogini E, Bartell SM, Manolagas SC. Oxidative stress stimulates apoptosis and activates NF-\u03baB in osteoblastic cells via a PKC\u03b2\/p66shc signaling cascade: counter regulation by estrogens or androgens. Mol Endocrinol. 2010;24:2030\u20137.","journal-title":"Mol Endocrinol."},{"key":"809_CR31","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1038\/nm.3586","volume":"20","author":"B Yu","year":"2014","unstructured":"Yu B, Chang J, Liu Y, Li J, Kevork K, Al-Hezaimi K, Graves DT, Park NH, Wang CY. Wnt4 signaling prevents skeletal aging and inflammation by inhibiting nuclear factor-\u03baB. Nat Med. 2014;20:1009\u201317.","journal-title":"Nat Med."},{"key":"809_CR32","doi-asserted-by":"publisher","first-page":"2707","DOI":"10.1002\/stem.2439","volume":"34","author":"C Jin","year":"2016","unstructured":"Jin C, Jia L, Huang Y, Zheng Y, Du N, Liu Y, Zhou Y. Inhibition of lncRNA MIR31HG promotes osteogenic differentiation of human adipose-derived stem cells. Stem Cells. 2016;34:2707\u201320.","journal-title":"Stem Cells."},{"key":"809_CR33","doi-asserted-by":"publisher","first-page":"S81","DOI":"10.1016\/S0092-8674(02)00703-1","volume":"109","author":"G Sankar","year":"2002","unstructured":"Sankar G, Michael K. Missing pieces in the NFkB puzzle. Cell. 2002;109:S81\u201396.","journal-title":"Cell."},{"key":"809_CR34","doi-asserted-by":"publisher","first-page":"1653","DOI":"10.1126\/science.1062374","volume":"293","author":"L Chen","year":"2001","unstructured":"Chen L, Fischle W, Verdin E, Greene W. Duration of nuclear NF-kappaB action regulated by reversible acetylation. Science. 2001;293:1653\u20137.","journal-title":"Science."},{"key":"809_CR35","doi-asserted-by":"publisher","first-page":"2927","DOI":"10.1073\/pnas.94.7.2927","volume":"94","author":"ME Gerritsen","year":"1997","unstructured":"Gerritsen ME, Williams AJ, Neish AS, Moore S, Shi Y, Collins T. CREB-binding protein\/p300 are transcriptional coactivators of p65. Proc Natl Acad Sci U S A. 1997;94:2927\u201332.","journal-title":"Proc Natl Acad Sci U S A."},{"key":"809_CR36","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1016\/S1097-2765(00)80066-0","volume":"1","author":"H Zhong","year":"1998","unstructured":"Zhong H, Voll RE, Ghosh S. Phosphorylation of NF-kappa B p65 by PKA stimulates transcriptional activity by promoting a novel bivalent interaction with the coactivator CBP\/p300. Mol Cell. 1998;1:661\u201371.","journal-title":"Mol Cell."},{"key":"809_CR37","doi-asserted-by":"publisher","first-page":"18972","DOI":"10.1073\/pnas.0910439106","volume":"106","author":"CK Ea","year":"2009","unstructured":"Ea CK, Baltimore D. Regulation of NF-kappaB activity through lysine monomethylation of p65. Proc Natl Acad Sci U S A. 2009;106:18972\u20137.","journal-title":"Proc Natl Acad Sci U S A."},{"key":"809_CR38","doi-asserted-by":"publisher","first-page":"15328","DOI":"10.1074\/jbc.M114.547349","volume":"289","author":"DP Harris","year":"2014","unstructured":"Harris DP, Bandyopadhyay S, Maxwell TJ, Willard B, DiCorleto PE. Tumor necrosis factor (TNF)-alpha induction of CXCL10 in endothelial cells requires protein arginine methyltransferase 5 (PRMT5)-mediated nuclear factor (NF)-kappaB p65 methylation. J Biol Chem. 2014;289:15328\u201339.","journal-title":"J Biol Chem."},{"key":"809_CR39","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1073\/pnas.0912493107","volume":"107","author":"T Lu","year":"2010","unstructured":"Lu T, Jackson M, Wang B, Yang M, Chance M, Miyagi M, et al. Regulation of NF-kappaB by NSD1\/FBXL11-dependent reversible lysine methylation of p65. Proc Natl Acad Sci U S A. 2010;107:46\u201351.","journal-title":"Proc Natl Acad Sci U S A."}],"container-title":["Stem Cell Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13287-018-0809-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13287-018-0809-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13287-018-0809-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,3,8]],"date-time":"2019-03-08T19:07:54Z","timestamp":1552072074000},"score":1,"resource":{"primary":{"URL":"https:\/\/stemcellres.biomedcentral.com\/articles\/10.1186\/s13287-018-0809-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,9]]},"references-count":39,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,12]]}},"alternative-id":["809"],"URL":"https:\/\/doi.org\/10.1186\/s13287-018-0809-1","relation":{},"ISSN":["1757-6512"],"issn-type":[{"value":"1757-6512","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,9]]},"assertion":[{"value":"19 September 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 January 2018","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 February 2018","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 March 2018","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This study was carried out in strict accordance with the recommendations of the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the Institutional Animal Care and Use Committee of the Peking University Health Science Center (approval no. LA2014233). All surgeries were performed under anesthesia, and all efforts were made to minimize animal suffering.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Publisher\u2019s Note"}}],"article-number":"65"}}