{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:34:11Z","timestamp":1791228851800,"version":"4.1.0"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2015,8,5]],"date-time":"2015-08-05T00:00:00Z","timestamp":1438732800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2015,8,5]],"date-time":"2015-08-05T00:00:00Z","timestamp":1438732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Osteoarthritis (OA) is characterized by degradation of articular cartilage and joint inflammation. MicroRNAs have been proved to play an important role in the regulation of chondrogenesis. Previous study showed that microRNA-210 (miR-210) was probably associated with osteoarthritis, while the function of miR-210 in osteoarthritis still remains unknown. The aim of the present study was to investigate the protective effect of miR-210 on osteoarthritis. In the <jats:italic>in vitro<\/jats:italic> study, miR-210 level in chondrocytes was decreased after treatment with lipopolysaccharide (LPS). Transfection with miR-210 mimic inhibited LPS-induced pro-inflammatory cytokines production, cell viability reduction and cell apoptosis. Results of luciferase activity assay showed that miR-210 targeted 3\u2032-UTR of death receptor 6 (DR6) to inhibit its expression. MiR-210 mimic and DR6 siRNA transfection inhibited the activation of NF-\u03baB pathway and cell apoptosis of chondrocytes. For the <jats:italic>in vivo<\/jats:italic> study, OA model was established on rats by anterior cruciate ligament transection (ACLT). MiR-210 expression is reduced in OA rats. MiR-210 over-expressing lentivirus was injected into the OA rats. Cytokines production and NF-\u03baB and DR6 expression in OA rats was inhibited by miR-210 overexpression. The results demonstrated that miR-210 decreased inflammation in articular cavity in OA rats by targeting DR6 and inhibiting NF-\u03baB signaling pathway.<\/jats:p>","DOI":"10.1038\/srep12775","type":"journal-article","created":{"date-parts":[[2015,8,5]],"date-time":"2015-08-05T12:36:17Z","timestamp":1438778177000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":92,"title":["MiR-210 inhibits NF-\u03baB signaling pathway by targeting DR6 in osteoarthritis"],"prefix":"10.1038","volume":"5","author":[{"given":"Dawei","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaorui","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangyue","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,8,5]]},"reference":[{"key":"BFsrep12775_CR1","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1016\/j.pop.2013.08.003","volume":"40","author":"RL Taruc-Uy","year":"2013","unstructured":"Taruc-Uy, R. L. & Lynch, S. A. Diagnosis and treatment of osteoarthritis. Prim Care. 40, 821\u2013836, vii (2013).","journal-title":"Prim Care."},{"key":"BFsrep12775_CR2","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1186\/ar3046","volume":"12","author":"MK Lotz","year":"2010","unstructured":"Lotz, M. K. & Kraus, V. B. New developments in osteoarthritis. Posttraumatic osteoarthritis: pathogenesis and pharmacological treatment options. Arthritis Res Ther. 12, 211 (2010).","journal-title":"Arthritis Res Ther."},{"key":"BFsrep12775_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1146\/annurev-bioeng-070909-105314","volume":"12","author":"W Sun","year":"2010","unstructured":"Sun, W. et al. microRNA: a master regulator of cellular processes for bioengineering systems. Annu Rev Biomed Eng. 12, 1\u201327 (2010).","journal-title":"Annu Rev Biomed Eng."},{"key":"BFsrep12775_CR4","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.cell.2005.06.036","volume":"122","author":"CM Croce","year":"2005","unstructured":"Croce, C. M. & Calin, G. A. miRNAs, cancer and stem cell division. Cell. 122, 6\u20137 (2005).","journal-title":"Cell."},{"key":"BFsrep12775_CR5","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1126\/science.1091903","volume":"303","author":"CZ Chen","year":"2004","unstructured":"Chen, C. Z., Li, L., Lodish, H. F. & Bartel, D. P. MicroRNAs modulate hematopoietic lineage differentiation. Science. 303, 83\u201386 (2004).","journal-title":"Science."},{"key":"BFsrep12775_CR6","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1038\/nrc1840","volume":"6","author":"A Esquela-Kerscher","year":"2006","unstructured":"Esquela-Kerscher, A. & Slack, F. J. Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 6, 259\u2013269 (2006).","journal-title":"Nat Rev Cancer."},{"key":"BFsrep12775_CR7","doi-asserted-by":"publisher","first-page":"18255","DOI":"10.1073\/pnas.0608791103","volume":"103","author":"E van Rooij","year":"2006","unstructured":"van Rooij, E. et al. A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure. Proc Natl Acad Sci U S A. 103, 18255\u201318260 (2006).","journal-title":"Proc Natl Acad Sci U S A."},{"key":"BFsrep12775_CR8","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1038\/nature03076","volume":"432","author":"MN Poy","year":"2004","unstructured":"Poy, M. N. et al. A pancreatic islet-specific microRNA regulates insulin secretion. Nature. 432, 226\u2013230 (2004).","journal-title":"Nature."},{"key":"BFsrep12775_CR9","doi-asserted-by":"publisher","first-page":"1284","DOI":"10.1002\/art.23429","volume":"58","author":"T Nakasa","year":"2008","unstructured":"Nakasa, T. et al. Expression of microRNA-146 in rheumatoid arthritis synovial tissue. Arthritis Rheum. 58, 1284\u20131292 (2008).","journal-title":"Arthritis Rheum."},{"key":"BFsrep12775_CR10","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1002\/art.23386","volume":"58","author":"J Stanczyk","year":"2008","unstructured":"Stanczyk, J. et al. Altered expression of MicroRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis. Arthritis Rheum. 58, 1001\u20131009 (2008).","journal-title":"Arthritis Rheum."},{"key":"BFsrep12775_CR11","doi-asserted-by":"publisher","first-page":"13","DOI":"10.3892\/ijmm.2014.1743","volume":"34","author":"C Wu","year":"2014","unstructured":"Wu, C. et al. MicroRNAs play a role in chondrogenesis and osteoarthritis (review). Int J Mol Med. 34, 13\u201323 (2014).","journal-title":"Int J Mol Med."},{"key":"BFsrep12775_CR12","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1002\/jor.22079","volume":"30","author":"K Yamasaki","year":"2012","unstructured":"Yamasaki, K. et al. Angiogenic microRNA-210 is present in cells surrounding osteonecrosis. J Orthop Res. 30, 1263\u20131270 (2012).","journal-title":"J Orthop Res."},{"key":"BFsrep12775_CR13","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1016\/j.febslet.2012.03.011","volume":"586","author":"J Qi","year":"2012","unstructured":"Qi, J., et al. microRNA-210 negatively regulates LPS-induced production of proinflammatory cytokines by targeting NF-kappaB1 in murine macrophages. FEBS Lett. 586, 1201\u20131207 (2012).","journal-title":"FEBS Lett."},{"key":"BFsrep12775_CR14","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/1741-7007-11-19","volume":"11","author":"AO Olarerin-George","year":"2013","unstructured":"Olarerin-George, A. O. et al. A functional genomics screen for microRNA regulators of NF-kappaB signaling. BMC Biol. 11, 19 (2013).","journal-title":"BMC Biol."},{"key":"BFsrep12775_CR15","doi-asserted-by":"publisher","first-page":"6758","DOI":"10.1038\/sj.onc.1209943","volume":"25","author":"MS Hayden","year":"2006","unstructured":"Hayden, M. S., West, A. P. & Ghosh, S. NF-kappaB and the immune response. Oncogene. 25, 6758\u20136780 (2006).","journal-title":"Oncogene."},{"key":"BFsrep12775_CR16","doi-asserted-by":"publisher","first-page":"6781","DOI":"10.1038\/sj.onc.1209944","volume":"25","author":"S Gerondakis","year":"2006","unstructured":"Gerondakis, S. et al. Unravelling the complexities of the NF-kappaB signalling pathway using mouse knockout and transgenic models. Oncogene. 25, 6781\u20136799(2006).","journal-title":"Oncogene."},{"key":"BFsrep12775_CR17","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1093\/jmcb\/mjr007","volume":"3","author":"X Ma","year":"2011","unstructured":"Ma, X., Becker Buscaglia, L. E., Barker, J. R. & Li, Y. MicroRNAs in NF-kappaB signaling. J Mol Cell Biol. 3, 159\u2013166 (2011).","journal-title":"J Mol Cell Biol."},{"key":"BFsrep12775_CR18","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/S0014-5793(98)00791-1","volume":"431","author":"G Pan","year":"1998","unstructured":"Pan, G. et al. Identification and functional characterization of DR6, a novel death domain-containing TNF receptor. FEBS Lett. 431, 351\u2013356 (1998).","journal-title":"FEBS Lett."},{"key":"BFsrep12775_CR19","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1016\/j.joca.2009.12.002","volume":"18","author":"C Karlsson","year":"2010","unstructured":"Karlsson, C. et al. Genome-wide expression profiling reveals new candidate genes associated with osteoarthritis. Osteoarthritis Cartilage. 18, 581\u2013592 (2010).","journal-title":"Osteoarthritis Cartilage."},{"key":"BFsrep12775_CR20","doi-asserted-by":"publisher","first-page":"741582","DOI":"10.1155\/2012\/741582","volume":"2012","author":"R Rainbow","year":"2012","unstructured":"Rainbow, R., Ren, W. & Zeng, L. Inflammation and Joint Tissue Interactions in OA: Implications for Potential Therapeutic Approaches. Arthritis. 2012, 741582 (2012).","journal-title":"Arthritis."},{"key":"BFsrep12775_CR21","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1101\/gad.1915510","volume":"24","author":"S Miyaki","year":"2010","unstructured":"Miyaki, S. et al. MicroRNA-140 plays dual roles in both cartilage development and homeostasis. Genes Dev. 24, 1173\u20131185 (2010).","journal-title":"Genes Dev."},{"key":"BFsrep12775_CR22","doi-asserted-by":"publisher","first-page":"e79","DOI":"10.1038\/emm.2013.152","volume":"46","author":"Y Zhang","year":"2014","unstructured":"Zhang, Y. et al. MicroRNA-21 controls the development of osteoarthritis by targeting GDF-5 in chondrocytes. Exp Mol Med. 46, e79 (2014).","journal-title":"Exp Mol Med."},{"key":"BFsrep12775_CR23","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1111\/j.1582-4934.2011.01291.x","volume":"16","author":"Y Zhang","year":"2012","unstructured":"Zhang, Y. et al. Elevated levels of hypoxia-inducible microRNA-210 in pre-eclampsia: new insights into molecular mechanisms for the disease. J Cell Mol Med. 16, 249\u2013259 (2012).","journal-title":"J Cell Mol Med."},{"key":"BFsrep12775_CR24","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1038\/nri2957","volume":"11","author":"LA O\u2019Neill","year":"2011","unstructured":"O\u2019Neill, L. A., Sheedy, F. J. & McCoy, C. E. MicroRNAs: the fine-tuners of Toll-like receptor signalling. Nat Rev Immunol. 11, 163\u2013175 (2011).","journal-title":"Nat Rev Immunol."},{"key":"BFsrep12775_CR25","first-page":"350419","volume":"2013","author":"J Qiu","year":"2013","unstructured":"Qiu, J. et al. Neuroprotective effects of microRNA-210 on hypoxic-ischemic encephalopathy. Biomed Res Int. 2013, 350419 (2013).","journal-title":"Biomed Res Int."},{"key":"BFsrep12775_CR26","doi-asserted-by":"publisher","first-page":"2111","DOI":"10.3892\/ijo.2014.2368","volume":"44","author":"L Li","year":"2014","unstructured":"Li, L. et al. Hypoxia-induced miR-210 in epithelial ovarian cancer enhances cancer cell viability via promoting proliferation and inhibiting apoptosis. Int J Oncol. 44, 2111\u20132120 (2014).","journal-title":"Int J Oncol."},{"key":"BFsrep12775_CR27","doi-asserted-by":"publisher","first-page":"e588","DOI":"10.1038\/cddis.2013.117","volume":"4","author":"JH Kim","year":"2013","unstructured":"Kim, J. H. et al. Reactive oxygen species-responsive miR-210 regulates proliferation and migration of adipose-derived stem cells via PTPN2. Cell Death Dis. 4, e588 (2013).","journal-title":"Cell Death Dis."},{"key":"BFsrep12775_CR28","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1016\/j.joca.2008.09.012","volume":"17","author":"SW Jones","year":"2009","unstructured":"Jones, S. W. et al. The identification of differentially expressed microRNA in osteoarthritic tissue that modulate the production of TNF-alpha and MMP13. Osteoarthritis Cartilage. 17, 464\u2013472 (2009).","journal-title":"Osteoarthritis Cartilage."},{"key":"BFsrep12775_CR29","doi-asserted-by":"publisher","first-page":"1410","DOI":"10.1007\/s00167-014-2955-z","volume":"23","author":"BM Cinar","year":"2015","unstructured":"Cinar, B. M. et al. Intra-articular zoledronic acid in a rat osteoarthritis model: significant reduced synovitis may indicate chondroprotective effect. Knee Surg Sports Traumatol Arthrosc. 23, 1410\u20131418 (2015).","journal-title":"Knee Surg Sports Traumatol Arthrosc."},{"key":"BFsrep12775_CR30","doi-asserted-by":"publisher","first-page":"2323","DOI":"10.1002\/art.38053","volume":"65","author":"MK Kosinska","year":"2013","unstructured":"Kosinska, M. K. et al. A lipidomic study of phospholipid classes and species in human synovial fluid. Arthritis Rheum. 65, 2323\u20132333 (2013).","journal-title":"Arthritis Rheum."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep12775","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep12775.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep12775.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T21:56:48Z","timestamp":1672955808000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep12775"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,8,5]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2015,10,16]]}},"alternative-id":["BFsrep12775"],"URL":"https:\/\/doi.org\/10.1038\/srep12775","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,8,5]]},"assertion":[{"value":"26 February 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 July 2015","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 August 2015","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"12775"}}