{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:05:10Z","timestamp":1792782310604,"version":"4.5.0"},"reference-count":46,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,10,18]],"date-time":"2018-10-18T00:00:00Z","timestamp":1539820800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Shandong Natural Science Foundation Project","award":["ZR2015HL067"],"award-info":[{"award-number":["ZR2015HL067"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>microRNA (miR) has been shown to be involved in the treatment of diseases such as osteoarthritis (OA). This study aims to investigate the role of miR\u2010206 in regulating insulin\u2010like growth factor\u20101 (IGF\u20101) in chondrocyte autophagy and apoptosis in an OA rat model via the phosphoinositide 3\u2010kinase (P13K)\/protein kinase B (AKT)\u2010mechanistic target of rapamycin (mTOR) signaling pathway. Wistar rats were used to establish the OA rat model, followed by the observation of histopathological changes, Mankin score, and the detection of IGF\u20101\u2010positive expression and tissue apoptosis. The underlying regulatory mechanisms of miR\u2010206 were analyzed in concert with treatment by an miR\u2010206 mimic, an miR\u2010206 inhibitor, or small interfering RNA against IGF\u20101 in chondrocytes isolated from OA rats. Then, the expression of miR\u2010206, IGF\u20101, and related factors in the signaling pathway, cell cycle, and apoptosis, as well as inflammatory factors, were determined. Subsequently, chondrocyte proliferation, cell cycle distribution, apoptosis, autophagy, and autolysosome were measured. OA articular cartilage tissue exhibited a higher Mankin score, promoted cell apoptotic rate, increased expression of IGF\u20101, Beclin1, light chain 3 (LC3), Unc\u201051\u2010like autophagy activating kinase 1 (ULK1), autophagy\u2010related 5 (Atg5), caspase\u20103, and Bax, yet exhibited decreased expression of miR\u2010206, P13K, AKT, mTOR, and Bcl\u20102. Besides, miR\u2010206 downregulated the expression of IGF\u20101 and activated the P13K\/AKT signaling pathway. Moreover, miR\u2010206 overexpression and IGF\u20101 silencing inhibited the interleukins levels (IL\u20106, IL\u201017, and IL\u201018), cell apoptotic rate, the formation of autolysosome, and cell autophagy while promoting the expression of IL\u20101\u03b2 and cell proliferation. The findings from our study provide a basis for the efficient treatment of OA by investigating the inhibitory effects of miR\u2010206 on autophagy and apoptosis of articular cartilage in OA via activating the IGF\u20101\u2010mediated PI3K\/AKT\u2010mTOR signaling pathway.<\/jats:p>","DOI":"10.1002\/jcb.27803","type":"journal-article","created":{"date-parts":[[2018,10,18]],"date-time":"2018-10-18T13:23:16Z","timestamp":1539868996000},"page":"5287-5303","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["microRNA\u2010206 is required for osteoarthritis development through its effect on apoptosis and autophagy of articular chondrocytes via modulating the phosphoinositide 3\u2010kinase\/protein kinase B\u2010mTOR pathway by targeting insulin\u2010like growth factor\u20101"],"prefix":"10.1002","volume":"120","author":[{"given":"Qian","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Joint Surgery &amp; Sports Medicine Qianfoshan Hospital of Shandong Province Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Liaocheng People\u2019s Hospital and Liaocheng Clinical School of Taishan Medical University Liaocheng China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"He","sequence":"additional","affiliation":[{"name":"Department of Blood Transfusion Shandong Provincial Hospital Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Geriatric Neurology Qianfoshan Hospital of Shandong Province Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8990-0109","authenticated-orcid":false,"given":"Xian\u2010Bo","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Joint Surgery &amp; Sports Medicine Qianfoshan Hospital of Shandong Province Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,10,18]]},"reference":[{"key":"e_1_2_7_1_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.23176"},{"key":"e_1_2_7_1_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24404"},{"key":"e_1_2_7_1_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204763"},{"key":"e_1_2_7_1_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.berh.2010.11.001"},{"key":"e_1_2_7_1_6_1","first-page":"17","article-title":"Improving joint pain and function in osteoarthritis","volume":"260","author":"Owens C","year":"2016","journal-title":"Practitioner"},{"key":"e_1_2_7_1_7_1","doi-asserted-by":"publisher","DOI":"10.1302\/2046-3758.611.BJR-2017-0090.R1"},{"key":"e_1_2_7_1_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2017.07.034"},{"key":"e_1_2_7_1_9_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2017.3021"},{"key":"e_1_2_7_1_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa074256"},{"key":"e_1_2_7_1_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1096781"},{"key":"e_1_2_7_1_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03702"},{"key":"e_1_2_7_1_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2012.128"},{"key":"e_1_2_7_1_14_1","doi-asserted-by":"publisher","DOI":"10.1302\/2046-3758.510.BJR-2016-0074.R2"},{"key":"e_1_2_7_1_15_1","doi-asserted-by":"publisher","DOI":"10.1159\/000487567"},{"key":"e_1_2_7_1_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.26248"},{"key":"e_1_2_7_1_17_1","first-page":"4493","article-title":"Correlation of insulin\u2010like growth factor 1 and osteoarthritic cartilage degradation: a spontaneous osteoarthritis in guinea\u2010pig","volume":"21","author":"Wei FY","year":"2017","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"e_1_2_7_1_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2006.10.004"},{"key":"e_1_2_7_1_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2087"},{"key":"e_1_2_7_1_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-018-4697-y"},{"key":"e_1_2_7_1_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-017-1420-0"},{"key":"e_1_2_7_1_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6989(89)90089-8"},{"key":"e_1_2_7_1_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2008.04.001"},{"key":"e_1_2_7_1_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-010-0458-z"},{"key":"e_1_2_7_1_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1263"},{"key":"e_1_2_7_1_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(04)00099-1"},{"key":"e_1_2_7_1_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-00302-8_3"},{"key":"e_1_2_7_1_28_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2011-200557"},{"key":"e_1_2_7_1_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.34323"},{"key":"e_1_2_7_1_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00264-012-1744-x"},{"key":"e_1_2_7_1_31_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1700-08.2009"},{"key":"e_1_2_7_1_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M302048200"},{"key":"e_1_2_7_1_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200007)43:7<1552::AID-ANR20>3.0.CO;2-W"},{"key":"e_1_2_7_1_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22254"},{"key":"e_1_2_7_1_35_1","doi-asserted-by":"publisher","DOI":"10.7314\/APJCP.2013.14.6.3751"},{"key":"e_1_2_7_1_36_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200603008"},{"key":"e_1_2_7_1_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2011.01.004"},{"key":"e_1_2_7_1_38_1","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.079590"},{"key":"e_1_2_7_1_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.02.097"},{"key":"e_1_2_7_1_40_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2016.5369"},{"key":"e_1_2_7_1_41_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20041636"},{"key":"e_1_2_7_1_42_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.056838"},{"key":"e_1_2_7_1_43_1","doi-asserted-by":"publisher","DOI":"10.2478\/s11658-011-0023-y"},{"key":"e_1_2_7_1_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24225"},{"key":"e_1_2_7_1_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.22604"},{"key":"e_1_2_7_1_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00774-005-0622-7"},{"key":"e_1_2_7_1_47_1","doi-asserted-by":"publisher","DOI":"10.5483\/BMBRep.2009.42.9.599"}],"container-title":["Journal of Cellular Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcb.27803","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcb.27803","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcb.27803","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcb.27803","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T16:50:07Z","timestamp":1715014207000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcb.27803"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,18]]},"references-count":46,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019,4]]}},"alternative-id":["10.1002\/jcb.27803"],"URL":"https:\/\/doi.org\/10.1002\/jcb.27803","archive":["Portico"],"relation":{},"ISSN":["0730-2312","1097-4644"],"issn-type":[{"value":"0730-2312","type":"print"},{"value":"1097-4644","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,18]]},"assertion":[{"value":"2018-03-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}