{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T09:40:18Z","timestamp":1768470018056,"version":"3.49.0"},"reference-count":40,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,3,13]],"date-time":"2021-03-13T00:00:00Z","timestamp":1615593600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Idiopathic short stature (ISS) is a main reason for low height among children. Its exact aetiology remains unclear. Recent findings have suggested that the aberrant expression of circRNAs in peripheral blood samples is associated with many diseases. However, to date, the role of aberrant circRNA expression in mediating ISS pathogenesis remains largely unknown. The up\u2010regulated circANAPC2 was identified by circRNA microarray analysis and RT\u2010qPCR. Overexpression of circANAPC2 inhibited the proliferation of human chondrocytes, and cell cycle was arrested in G1 phase. The expressions of collagen type X, RUNX2, OCN and OPN were significantly down\u2010regulated following circANAPC2 overexpression. Moreover, Von Kossa staining intensity and alkaline phosphatase activity were also decreased. Luciferase reporter assay results showed that circANAPC2 could be targeted by miR\u2010874\u20103p. CircANAPC2 overexpression in human chondrocytes inhibits the expression of miR\u2010874\u20103p. The co\u2010localization of circANAPC2 and miR\u2010874\u20103p was confirmed in both human chondrocytes and murine femoral growth plates via in situ hybridization. The rescue experiment demonstrated that the high expression of miR\u2010874\u20103p overexpression antagonized the suppression of endochondral ossification, hypertrophy and chondrocyte growth caused by circANAPC2 overexpression. A high\u2010throughput screening of mRNA expression and RT\u2010qPCR verified SMAD3 demonstrated the highest different expressions following overcircANAPC2. Luciferase reporter assay results indicated that miR\u2010874\u20103p could be targeted by Smad3, thus down\u2010regulating the expression of Smad3. Subsequent rescue experiments of SMAD3 further confirmed that circANAPC2 suppresses endochondral ossification, hypertrophy and chondrocyte growth through miR\u2010874\u20103p\/Smad3 axis. The present study provides evidence that circANAPC2 can serve as a promising target for ISS treatment.<\/jats:p>","DOI":"10.1111\/jcmm.16419","type":"journal-article","created":{"date-parts":[[2021,3,13]],"date-time":"2021-03-13T18:36:51Z","timestamp":1615660611000},"page":"3408-3426","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Circular RNA circANAPC2 mediates the impairment of endochondral ossification by miR\u2010874\u20103p\/SMAD3 signalling pathway in idiopathic short stature"],"prefix":"10.1111","volume":"25","author":[{"given":"Xijuan","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pediatrics The Second Affiliated Hospital of Nanchang University Nanchang City China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The Second Affiliated Hospital of Nanchang University Nanchang City China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuan","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The Second Affiliated Hospital of Nanchang University Nanchang City China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianle","family":"Sheng","sequence":"additional","affiliation":[{"name":"Department of Molecular laboratory The Second Affiliated Hospital of Nanchang University Nanchang City China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinghong","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The Second Affiliated Hospital of Nanchang University Nanchang City China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7128-2621","authenticated-orcid":false,"given":"Jingyu","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The Second Affiliated Hospital of Nanchang University Nanchang City China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,3,13]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1159\/000502901"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2013.71"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2431-5-15"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2009-3609"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201200131"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-09-0880"},{"key":"e_1_2_9_8_1","first-page":"113","article-title":"Growth hormone treatment for idiopathic short stature","volume":"16","author":"Cutfield WS","year":"2018","journal-title":"Pediatr Endocrinol Rev"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ghir.2018.09.003"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-1995"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000737"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40618-017-0786-8"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2016-103758"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2017.00038"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11928"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1159\/000495589"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes8120353"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3349\/ymj.2018.59.3.349"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-017-0598-7"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-019-1041-z"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.14400"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2019.01.006"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.24713"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2020.115368"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3658"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1938"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18102054"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2019.03.037"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2019.10.026"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-019-00120-z"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2020.02.134"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2018.09.187"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1359\/JBMR.050911"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006352"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21186665"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2018.0071"},{"key":"e_1_2_9_37_1","first-page":"789","article-title":"The inhibitory roles of Ihh downregulation on chondrocyte growth and differentiation","volume":"15","author":"Deng A","year":"2018","journal-title":"Exp Therap Med"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.3.543"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600729"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12794"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.28733"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.16419","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jcmm.16419","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.16419","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T08:19:37Z","timestamp":1692605977000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.16419"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,13]]},"references-count":40,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2021,4]]}},"alternative-id":["10.1111\/jcmm.16419"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.16419","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,13]]},"assertion":[{"value":"2020-09-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}