{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:32:47Z","timestamp":1790667167636,"version":"4.1.0"},"reference-count":58,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,6,3]],"date-time":"2021-06-03T00:00:00Z","timestamp":1622678400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,6,3]],"date-time":"2021-06-03T00:00:00Z","timestamp":1622678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81802193"],"award-info":[{"award-number":["81802193"]}],"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":["81822012, 81771043"],"award-info":[{"award-number":["81822012, 81771043"]}],"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":["9204920005, 81722031, 81770873"],"award-info":[{"award-number":["9204920005, 81722031, 81770873"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Long noncoding RNAs are widely implicated in diverse disease processes. Nonetheless, their regulatory roles in bone resorption are undefined. Here, we identify lncRNA Nron as a critical suppressor of bone resorption. We demonstrate that osteoclastic Nron knockout mice exhibit an osteopenia phenotype with elevated bone resorption activity. Conversely, osteoclastic Nron transgenic mice exhibit lower bone resorption and higher bone mass. Furthermore, the pharmacological overexpression of Nron inhibits bone resorption, while caused apparent side effects in mice. To minimize the side effects, we further identify a functional motif of Nron. The delivery of Nron functional motif to osteoclasts effectively reverses bone loss without obvious side effects. Mechanistically, the functional motif of Nron interacts with E3 ubiquitin ligase CUL4B to regulate ER\u03b1 stability. These results indicate that Nron is a key bone resorption suppressor, and the lncRNA functional motif could potentially be utilized to treat diseases with less risk of side effects.<\/jats:p>","DOI":"10.1038\/s41467-021-23642-7","type":"journal-article","created":{"date-parts":[[2021,6,3]],"date-time":"2021-06-03T06:15:03Z","timestamp":1622700903000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["A functional motif of long noncoding RNA Nron against osteoporosis"],"prefix":"10.1038","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7314-0085","authenticated-orcid":false,"given":"Fujun","family":"Jin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Biao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangning","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingxiang","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meijing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cui","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3401-369X","authenticated-orcid":false,"given":"Rui","family":"Yue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yexuan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renfa","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuolin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xunming","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huawei","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiduo","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9918-2865","authenticated-orcid":false,"given":"Yifei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4323-0506","authenticated-orcid":false,"given":"Yao","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9798-834X","authenticated-orcid":false,"given":"Xiaogang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,3]]},"reference":[{"key":"23642_CR1","doi-asserted-by":"publisher","DOI":"10.1007\/s11657-018-0549-y","volume":"14","author":"F Yu","year":"2019","unstructured":"Yu, F. & Xia, W. The epidemiology of osteoporosis, associated fragility fractures, and management gap in China. Arch. Osteoporos. 14, 32 (2019).","journal-title":"Arch. Osteoporos."},{"key":"23642_CR2","doi-asserted-by":"publisher","first-page":"1761","DOI":"10.1016\/S0140-6736(02)08657-9","volume":"359","author":"SR Cummings","year":"2002","unstructured":"Cummings, S. R. & Melton, L. J. Epidemiology and outcomes of osteoporotic fractures. Lancet 359, 1761\u20131767 (2002).","journal-title":"Lancet"},{"key":"23642_CR3","doi-asserted-by":"publisher","first-page":"S15","DOI":"10.1038\/550S15a","volume":"550","author":"C Brown","year":"2017","unstructured":"Brown, C. Osteoporosis: staying strong. Nature 550, S15\u2013S17 (2017).","journal-title":"Nature"},{"key":"23642_CR4","doi-asserted-by":"publisher","first-page":"2024","DOI":"10.1002\/med.21504","volume":"38","author":"H Awasthi","year":"2018","unstructured":"Awasthi, H., Mani, D., Singh, D. & Gupta, A. The underlying pathophysiology and therapeutic approaches for osteoporosis. Med. Res. Rev. 38, 2024\u20132057 (2018).","journal-title":"Med. Res. Rev."},{"key":"23642_CR5","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s40199-017-0167-z","volume":"25","author":"O Tabatabaei-Malazy","year":"2017","unstructured":"Tabatabaei-Malazy, O., Salari, P., Khashayar, P. & Larijani, B. New horizons in treatment of osteoporosis. Daru 25, 2 (2017).","journal-title":"Daru"},{"key":"23642_CR6","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1016\/S0140-6736(18)32112-3","volume":"393","author":"JE Compston","year":"2019","unstructured":"Compston, J. E., McClung, M. R. & Leslie, W. D. Osteoporosis. Lancet 393, 364\u2013376 (2019).","journal-title":"Lancet"},{"key":"23642_CR7","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1534\/genetics.112.146704","volume":"193","author":"JT Kung","year":"2013","unstructured":"Kung, J. T., Colognori, D. & Lee, J. T. Long noncoding RNAs: past, present, and future. Genetics 193, 651\u2013669 (2013).","journal-title":"Genetics"},{"key":"23642_CR8","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1038\/s41556-019-0311-8","volume":"21","author":"RW Yao","year":"2019","unstructured":"Yao, R. W., Wang, Y. & Chen, L. L. Cellular functions of long noncoding RNAs. Nat. Cell Biol. 21, 542\u2013551 (2019).","journal-title":"Nat. Cell Biol."},{"key":"23642_CR9","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1016\/j.cmet.2019.08.013","volume":"30","author":"J Kim","year":"2019","unstructured":"Kim, J. & DeBerardinis, R. J. Mechanisms and implications of metabolic heterogeneity in cancer. Cell Metab. 30, 434\u2013446 (2019).","journal-title":"Cell Metab."},{"key":"23642_CR10","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.molmed.2018.01.001","volume":"24","author":"G Arun","year":"2018","unstructured":"Arun, G., Diermeier, S. D. & Spector, D. L. Therapeutic targeting of long non-coding RNAs in cancer. Trends Mol. Med. 24, 257\u2013277 (2018).","journal-title":"Trends Mol. Med."},{"key":"23642_CR11","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1152\/physrev.00041.2015","volume":"96","author":"J Beermann","year":"2016","unstructured":"Beermann, J., Piccoli, M. T., Viereck, J. & Thum, T. Non-coding RNAs in development and disease: background, mechanisms, and therapeutic approaches. Physiol. Rev. 96, 1297\u20131325 (2016).","journal-title":"Physiol. Rev."},{"key":"23642_CR12","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/j.tcb.2011.04.001","volume":"21","author":"O Wapinski","year":"2011","unstructured":"Wapinski, O. & Chang, H. Y. Long noncoding RNAs and human disease. Trends Cell Biol. 21, 354\u2013361 (2011).","journal-title":"Trends Cell Biol."},{"key":"23642_CR13","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.cmet.2019.11.010","volume":"31","author":"MT Snaebjornsson","year":"2020","unstructured":"Snaebjornsson, M. T., Janaki-Raman, S. & Schulze, A. Greasing the wheels of the cancer machine: the role of lipid metabolism in cancer. Cell Metab. 31, 62\u201376 (2020).","journal-title":"Cell Metab."},{"key":"23642_CR14","doi-asserted-by":"publisher","first-page":"1559","DOI":"10.1016\/j.cell.2017.11.040","volume":"171","author":"Y Hosono","year":"2017","unstructured":"Hosono, Y. et al. Oncogenic role of THOR, a conserved cancer\/testis long non-coding RNA. Cell 171, 1559\u20131572 (2017). e1520.","journal-title":"Cell"},{"key":"23642_CR15","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1016\/j.stemcr.2018.01.014","volume":"10","author":"A Fiorenzano","year":"2018","unstructured":"Fiorenzano, A. et al. An ultraconserved element containing lncRNA preserves transcriptional dynamics and maintains ESC self-renewal. Stem Cell Rep. 10, 1102\u20131114 (2018).","journal-title":"Stem Cell Rep."},{"key":"23642_CR16","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1016\/j.molcel.2014.01.021","volume":"53","author":"N Lin","year":"2014","unstructured":"Lin, N. et al. An evolutionarily conserved long noncoding RNA TUNA controls pluripotency and neural lineage commitment. Mol. Cell 53, 1005\u20131019 (2014).","journal-title":"Mol. Cell"},{"key":"23642_CR17","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/j.cell.2010.06.040","volume":"142","author":"M Huarte","year":"2010","unstructured":"Huarte, M. et al. A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell 142, 409\u2013419 (2010).","journal-title":"Cell"},{"key":"23642_CR18","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1126\/science.1192002","volume":"329","author":"MC Tsai","year":"2010","unstructured":"Tsai, M. C. et al. Long noncoding RNA as modular scaffold of histone modification complexes. Science 329, 689\u2013693 (2010).","journal-title":"Science"},{"key":"23642_CR19","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6395","volume":"5","author":"WH Hudson","year":"2014","unstructured":"Hudson, W. H. et al. Conserved sequence-specific lincRNA-steroid receptor interactions drive transcriptional repression and direct cell fate. Nat. Commun. 5, 5395 (2014).","journal-title":"Nat. Commun."},{"key":"23642_CR20","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1038\/s41413-019-0048-9","volume":"7","author":"AM Silva","year":"2019","unstructured":"Silva, A. M. et al. Long noncoding RNAs: a missing link in osteoporosis. Bone Res. 7, 10 (2019).","journal-title":"Bone Res."},{"key":"23642_CR21","doi-asserted-by":"publisher","first-page":"5251","DOI":"10.1172\/JCI99044","volume":"128","author":"C-J Li","year":"2018","unstructured":"Li, C.-J. et al. Long noncoding RNA Bmncr regulates mesenchymal stem cell fate during skeletal aging. J. Clin. Invest. 128, 5251\u20135266 (2018).","journal-title":"J. Clin. Invest."},{"key":"23642_CR22","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1016\/j.ymthe.2018.11.019","volume":"27","author":"L Yang","year":"2019","unstructured":"Yang, L. et al. The long non-coding RNA-ORLNC1 regulates bone mass by directing mesenchymal stem cell fate. Mol. Ther. 27, 394\u2013410 (2019).","journal-title":"Mol. Ther."},{"key":"23642_CR23","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1038\/s42255-019-0053-8","volume":"1","author":"Y Sun","year":"2019","unstructured":"Sun, Y. et al. The long noncoding RNA lnc-ob1 facilitates bone formation by upregulating Osterix in osteoblasts. Nat. Metab. 1, 485\u2013496 (2019).","journal-title":"Nat. Metab."},{"key":"23642_CR24","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1159\/000488474","volume":"46","author":"H Quan","year":"2018","unstructured":"Quan, H. et al. LncRNA-AK131850 sponges MiR-93-5p in newborn and mature osteoclasts to enhance the secretion of vascular endothelial growth factor a promoting vasculogenesis of endothelial progenitor cells. Cell. Physiol. Biochem. 46, 401\u2013417 (2018).","journal-title":"Cell. Physiol. Biochem."},{"key":"23642_CR25","doi-asserted-by":"publisher","first-page":"2291","DOI":"10.1159\/000491539","volume":"47","author":"Y Wang","year":"2018","unstructured":"Wang, Y., Luo, T. B., Liu, L. & Cui, Z. Q. LncRNA LINC00311 promotes the proliferation and differentiation of osteoclasts in osteoporotic rats through the notch signaling pathway by targeting DLL3. Cell. Physiol. Biochem. 47, 2291\u20132306 (2018).","journal-title":"Cell. Physiol. Biochem."},{"key":"23642_CR26","doi-asserted-by":"publisher","first-page":"115072","DOI":"10.1016\/j.bone.2019.115072","volume":"130","author":"Y Chang","year":"2020","unstructured":"Chang, Y. et al. LncRNA expression profiles and the negative regulation of lncRNA-NOMMUT037835.2 in osteoclastogenesis. Bone 130, 115072 (2020).","journal-title":"Bone"},{"key":"23642_CR27","doi-asserted-by":"publisher","first-page":"587","DOI":"10.3389\/fendo.2018.00587","volume":"9","author":"QY Wu","year":"2018","unstructured":"Wu, Q. Y. et al. Long non-coding RNAs: a new regulatory code for osteoporosis. Front. Endocrinol. (Lausanne) 9, 587 (2018).","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"23642_CR28","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1016\/j.ajhg.2011.03.008","volume":"88","author":"Q Zhu","year":"2011","unstructured":"Zhu, Q. et al. A genome-wide comparison of the functional properties of rare and common genetic variants in humans. Am. J. Hum. Genet. 88, 458\u2013468 (2011).","journal-title":"Am. J. Hum. Genet."},{"key":"23642_CR29","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/j.ejphar.2015.03.028","volume":"759","author":"T Komori","year":"2015","unstructured":"Komori, T. Animal models for osteoporosis. Eur. J. Pharmacol. 759, 287\u2013294 (2015).","journal-title":"Eur. J. Pharmacol."},{"key":"23642_CR30","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1007\/s12018-015-9185-x","volume":"13","author":"N Gua\u00f1abens","year":"2015","unstructured":"Gua\u00f1abens, N., Peris, P. & Monegal, A. Bone turnover markers: a clinical review. Clin. Rev. Bone Miner. Metab. 13, 83\u201397 (2015).","journal-title":"Clin. Rev. Bone Miner. Metab."},{"key":"23642_CR31","doi-asserted-by":"publisher","first-page":"1570","DOI":"10.1126\/science.1115901","volume":"309","author":"AT Willingham","year":"2005","unstructured":"Willingham, A. T. et al. A strategy for probing the function of noncoding RNAs finds a repressor of NFAT. Science 309, 1570\u20131573 (2005).","journal-title":"Science"},{"key":"23642_CR32","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1038\/nature05683","volume":"446","author":"F Ohtake","year":"2007","unstructured":"Ohtake, F. et al. Dioxin receptor is a ligand-dependent E3 ubiquitin ligase. Nature 446, 562\u2013566 (2007).","journal-title":"Nature"},{"key":"23642_CR33","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1016\/j.cell.2007.07.025","volume":"130","author":"T Nakamura","year":"2007","unstructured":"Nakamura, T. et al. Estrogen prevents bone loss via estrogen receptor alpha and induction of Fas ligand in osteoclasts. Cell 130, 811\u2013823 (2007).","journal-title":"Cell"},{"key":"23642_CR34","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1152\/physrev.00033.2015","volume":"97","author":"M Almeida","year":"2017","unstructured":"Almeida, M. et al. Estrogens and androgens in skeletal physiology and pathophysiology. Physiol. Rev. 97, 135\u2013187 (2017).","journal-title":"Physiol. Rev."},{"key":"23642_CR35","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1038\/nrc3622","volume":"14","author":"W Zhou","year":"2013","unstructured":"Zhou, W. & Slingerland, J. M. Links between oestrogen receptor activation and proteolysis: relevance to hormone-regulated cancer therapy. Nat. Rev. Cancer 14, 26\u201338 (2013).","journal-title":"Nat. Rev. Cancer"},{"key":"23642_CR36","doi-asserted-by":"publisher","first-page":"7469","DOI":"10.2147\/IJN.S139775","volume":"12","author":"M Cai","year":"2017","unstructured":"Cai, M. et al. A bone-resorption surface-targeting nanoparticle to deliver anti-miR214 for osteoporosis therapy. Int. J. Nanomed. 12, 7469\u20137482 (2017).","journal-title":"Int. J. Nanomed."},{"key":"23642_CR37","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.cbi.2004.09.008","volume":"150","author":"AP Li","year":"2004","unstructured":"Li, A. P. Accurate prediction of human drug toxicity: a major challenge in drug development. Chem. Biol. Interact. 150, 3\u20137 (2004).","journal-title":"Chem. Biol. Interact."},{"key":"23642_CR38","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1038\/nm.4179","volume":"22","author":"Z Wang","year":"2016","unstructured":"Wang, Z. et al. The long noncoding RNA Chaer defines an epigenetic checkpoint in cardiac hypertrophy. Nat. Med. 22, 1131\u20131139 (2016).","journal-title":"Nat. Med."},{"key":"23642_CR39","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-017-1331-y","volume":"18","author":"O Marin-Bejar","year":"2017","unstructured":"Marin-Bejar, O. et al. The human lncRNA LINC-PINT inhibits tumor cell invasion through a highly conserved sequence element. Genome Biol. 18, 202 (2017).","journal-title":"Genome Biol."},{"key":"23642_CR40","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1016\/S0140-6736(10)62349-5","volume":"377","author":"TD Rachner","year":"2011","unstructured":"Rachner, T. D., Khosla, S. & Hofbauer, L. C. Osteoporosis: now and the future. Lancet 377, 1276\u20131287 (2011).","journal-title":"Lancet"},{"key":"23642_CR41","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1016\/j.stem.2010.10.004","volume":"7","author":"SL Teitelbaum","year":"2010","unstructured":"Teitelbaum, S. L. Stem cells and osteoporosis therapy. Cell Stem Cell 7, 553\u2013554 (2010).","journal-title":"Cell Stem Cell"},{"key":"23642_CR42","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1158\/2159-8290.CD-11-0209","volume":"1","author":"JR Prensner","year":"2011","unstructured":"Prensner, J. R. & Chinnaiyan, A. M. The emergence of lncRNAs in cancer biology. Cancer Discov. 1, 391\u2013407 (2011).","journal-title":"Cancer Discov."},{"key":"23642_CR43","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.1016\/j.jacc.2015.12.051","volume":"67","author":"RA Boon","year":"2016","unstructured":"Boon, R. A., Ja\u00e9, N., Holdt, L. & Dimmeler, S. Long noncoding RNAs: from clinical genetics to therapeutic targets? J. Am. Coll. Cardiol. 67, 1214\u20131226 (2016).","journal-title":"J. Am. Coll. Cardiol."},{"key":"23642_CR44","doi-asserted-by":"publisher","first-page":"1606","DOI":"10.1002\/jcp.27031","volume":"234","author":"C Liu","year":"2019","unstructured":"Liu, C. et al. LncRNA AK077216 promotes RANKL-induced osteoclastogenesis and bone resorption via NFATc1 by inhibition of NIP45. J. Cell. Physiol. 234, 1606\u20131617 (2019).","journal-title":"J. Cell. Physiol."},{"key":"23642_CR45","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1002\/tox.22672","volume":"34","author":"CP Lee","year":"2019","unstructured":"Lee, C. P., Huang, Y. N., Nithiyanantham, S., Huang, C. M. & Ko, Y. C. LncRNA-Jak3:Jak3 coexpressed pattern regulates monosodium urate crystal-induced osteoclast differentiation through Nfatc1\/Ctsk expression. Environ. Toxicol. 34, 179\u2013187 (2019).","journal-title":"Environ. Toxicol."},{"key":"23642_CR46","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-10-122","volume":"10","author":"C Unzu","year":"2012","unstructured":"Unzu, C. et al. Transient and intensive pharmacological immunosuppression fails to improve AAV-based liver gene transfer in non-human primates. J. Transl. Med. 10, 122 (2012).","journal-title":"J. Transl. Med."},{"key":"23642_CR47","doi-asserted-by":"publisher","first-page":"2358","DOI":"10.1038\/s41418-019-0306-9","volume":"26","author":"YJ Moon","year":"2019","unstructured":"Moon, Y. J. et al. Sirtuin 6 in preosteoclasts suppresses age- and estrogen deficiency-related bone loss by stabilizing estrogen receptor alpha. Cell Death Differ. 26, 2358\u20132370 (2019).","journal-title":"Cell Death Differ."},{"key":"23642_CR48","first-page":"1987","volume":"22","author":"HB Hu","year":"2018","unstructured":"Hu, H. B., Chen, Q. & Ding, S. Q. LncRNA LINC01116 competes with miR-145 for the regulation of ESR1 expression in breast cancer. Eur. Rev. Med. Pharmacol. Sci. 22, 1987\u20131993 (2018).","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"23642_CR49","doi-asserted-by":"publisher","first-page":"1518","DOI":"10.1159\/000495643","volume":"51","author":"P Basak","year":"2018","unstructured":"Basak, P. et al. Long non-coding RNA H19 acts as an estrogen receptor modulator that is required for endocrine therapy resistance in ER+ breast cancer cells. Cell. Physiol. Biochem. 51, 1518\u20131532 (2018).","journal-title":"Cell. Physiol. Biochem."},{"key":"23642_CR50","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1111\/nyas.13523","volume":"1410","author":"AM Rooney","year":"2017","unstructured":"Rooney, A. M. & van der Meulen, M. C. H. Mouse models to evaluate the role of estrogen receptor alpha in skeletal maintenance and adaptation. Ann. N. Y. Acad. Sci. 1410, 85\u201392 (2017).","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"23642_CR51","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1038\/nrendo.2013.179","volume":"9","author":"SC Manolagas","year":"2013","unstructured":"Manolagas, S. C., O\u2019Brien, C. A. & Almeida, M. The role of estrogen and androgen receptors in bone health and disease. Nat. Rev. Endocrinol. 9, 699\u2013712 (2013).","journal-title":"Nat. Rev. Endocrinol."},{"key":"23642_CR52","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1021\/bc7002132","volume":"18","author":"D Wang","year":"2007","unstructured":"Wang, D. et al. Osteotropic peptide that differentiates functional domains of the skeleton. Bioconjug. Chem. 18, 1375\u20131378 (2007).","journal-title":"Bioconjug. Chem."},{"key":"23642_CR53","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/j.biomaterials.2015.02.007","volume":"52","author":"J Liu","year":"2015","unstructured":"Liu, J. et al. A delivery system specifically approaching bone resorption surfaces to facilitate therapeutic modulation of microRNAs in osteoclasts. Biomaterials 52, 148\u2013160 (2015).","journal-title":"Biomaterials"},{"key":"23642_CR54","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.ijpharm.2013.04.063","volume":"450","author":"JY Cherng","year":"2013","unstructured":"Cherng, J. Y., Hou, T. Y., Shih, M. F., Talsma, H. & Hennink, W. E. Polyurethane-based drug delivery systems. Int. J. Pharm. 450, 145\u2013162 (2013).","journal-title":"Int. J. Pharm."},{"key":"23642_CR55","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1002\/jbmr.1805","volume":"28","author":"DW Dempster","year":"2013","unstructured":"Dempster, D. W. et al. Standardized nomenclature, symbols, and units for bone histomorphometry: a 2012 update of the report of the ASBMR Histomorphometry Nomenclature Committee. J. Bone Miner. Res. 28, 2\u201317 (2013).","journal-title":"J. Bone Miner. Res."},{"key":"23642_CR56","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1038\/s41591-018-0005-y","volume":"24","author":"S Weske","year":"2018","unstructured":"Weske, S. et al. Targeting sphingosine-1-phosphate lyase as an anabolic therapy for bone loss. Nat. Med. 24, 667\u2013678 (2018).","journal-title":"Nat. Med."},{"key":"23642_CR57","doi-asserted-by":"publisher","first-page":"1799","DOI":"10.1002\/jbmr.3479","volume":"33","author":"S Yang","year":"2018","unstructured":"Yang, S. et al. Suppression of bone resorption by miR-141 in aged Rhesus monkeys. J. Bone Miner. Res. 33, 1799\u20131812 (2018).","journal-title":"J. Bone Miner. Res."},{"key":"23642_CR58","doi-asserted-by":"publisher","first-page":"8380","DOI":"10.3892\/mmr.2017.7625","volume":"16","author":"ZH Li","year":"2017","unstructured":"Li, Z. H. et al. High-dose PMA with RANKL and MCSF induces THP1 cell differentiation into human functional osteoclasts in vitro. Mol. Med. Rep. 16, 8380\u20138384 (2017).","journal-title":"Mol. Med. Rep."}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-021-23642-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-021-23642-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-021-23642-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T08:03:16Z","timestamp":1781596996000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-021-23642-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,3]]},"references-count":58,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["23642"],"URL":"https:\/\/doi.org\/10.1038\/s41467-021-23642-7","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,3]]},"assertion":[{"value":"29 March 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 April 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 June 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 June 2026","order":5,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Clarification","order":6,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Editor\u2019s Note: Readers are alerted that concerns have been raised regarding the reliability of data presented in this article. Further editorial action will be taken if appropriate once the investigation into the concerns is complete and all parties have been given an opportunity to respond in full.","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"3319"}}