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The tumor\u2010associated long noncoding RNA expressed on chromosome 2 (TALNEC2) overexpression or silencing vectors (pTALNEC2 or si\u2010TALNEC2) was utilized for MC3T3\u2010E1 cell transfection. Viability and apoptosis rate were individually tested by cell counting kit\u20108 and Annexin V\u2010fluorescein isothiocyanate\/propidium iodide kit untied with flow cytometry. The alkaline phosphatase activity (ALP) activity was tested through ALP assay. The quantitative reverse transcription PCR or Western blot was performed for elements detection at the RNA or protein level. Hypoxia treatment induced viability inhibition and CyclinD1 reduction, but elevation of p53 and p16. It also promoted apoptosis by increasing apoptotic cells, Bax, and cleaved\u2010poly ADP\u2010ribose polymerase but decreasing Bcl\u20102. Also, hypoxia stimuli restrained ALP activity, and osteopontin, osteocalcin, and Runt\u2010related transcription factor 2 expression. Those effects caused by hypoxia stimuli were all reversed by ICA. TALNEC2 was downregulated by ICA, whose impacts were subsequently abolished by pTALNEC2. Silencing TALNEC2 displayed similar effects with ICA. But the apoptosis was not affected by si\u2010TALNEC2. ICA blocked ste20\u2010related proline\/alanine\u2010rich kinase\/c\u2010Jun N\u2010terminal kinase (SPAK\/JNK) but triggered phosphatidylinositol 3\u2010kinase\/protein kinase B\/mammalian target of rapamycin (PI3K\/AKT\/mTOR) pathway in MC3T3\u2010E1 cell by suppressing TALNEC2. ICA relieved hypoxia\u2010stimulated damage by restraining TALNEC2 through blocking SPAK\/JNK and triggering PI3K\/AKT\/mTOR in the MC3T3\u2010E1 cell.<\/jats:p>","DOI":"10.1002\/bab.1874","type":"journal-article","created":{"date-parts":[[2019,12,17]],"date-time":"2019-12-17T09:00:16Z","timestamp":1576573216000},"page":"1000-1010","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Icariin alleviates hypoxia\u2010induced damage in MC3T3\u2010E1 cells by downregulating TALNEC2"],"prefix":"10.1002","volume":"67","author":[{"given":"Weiguo","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Orthopaedics The Affiliated Hospital of Shandong University of Traditional Chinese Medicine  Jinan People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Xin","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The Affiliated Hospital of Shandong University of Traditional Chinese Medicine  Jinan People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenming","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The Affiliated Hospital of Shandong University of Traditional Chinese Medicine  Jinan People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lizhong","family":"Jing","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The Affiliated Hospital of Shandong University of Traditional Chinese Medicine  Jinan People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7202-8780","authenticated-orcid":false,"given":"Peng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The Affiliated Hospital of Shandong University of Traditional Chinese Medicine  Jinan People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,2,7]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-017-4255-1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00264-018-3917-8"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1302\/2058-5241.4.180036"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3109\/14397595.2014.932038"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.5027"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24158"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12013-013-9533-8"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2010.04.003"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2013.05.039"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.12147"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-13-504"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R116.760884"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-10-38"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/6857042"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.29161"},{"key":"e_1_2_9_17_1","volume":"39","author":"Zhang Y.","year":"2019","journal-title":"Biosci. 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