{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T01:27:49Z","timestamp":1791854869459,"version":"4.3.4"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T00:00:00Z","timestamp":1613952000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Orthopaedic Surgery"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>The current study investigated the role of CircCDR1as on angiogenesis of bone microvascular endothelial cells (BMECs) isolated from non\u2010traumatic ONFH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Forty corticosteroid\u2010induced ONFH patients received THA were enrolled in our study. Expressions of CircCDR1as, miR\u2010135b, and FIH\u20101 were detected by qRT\u2010PCR in affected necrosis tissue and non\u2010affected normal tissue. Bone microvascular endothelial cells (BMEC) were isolated from six patients and treated with 0.1\u2009mg\/mL hydrocortisone to establish a GC\u2010damaged model of BMECs. Circ CDR1as plasmid and miR\u2010135b mimic were transfected into BMECs. BMEC proliferation was assessed using MTT assays. The migration ability of cells was detected by scratch\u2010wound assays. Matrigel assay was performed to detect angiogenesis <jats:italic>in vitro<\/jats:italic>. Western blot assay was used to detect HIF\u20101\u03b1, VEGF, and FIH\u20101 expressions. FISH, RNA pull down, RIP, and luciferase assay were carried out to determine the interaction of CircCDR1as, miR\u2010135b, and FIH\u20101.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CircCDR1as was upregulated(2.02\u2009\u00b1\u20090.30 <jats:italic>vs<\/jats:italic>. 1.00\u2009\u00b1\u20090.10,<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) whereas miR\u2010135b was downregulated (0.55\u2009\u00b1\u20090.12 <jats:italic>vs<\/jats:italic>. 1.00\u2009\u00b1\u20090.10,<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) in affected tissues than in non\u2010affected tissues. Expression of CircCDR1as and FIH\u20101 were negatively associated with miR\u2010135b in affected tissues (CircCDR1as with miR\u2010135b: r = \u22120.506, P\u2009&lt;\u20090.001; FIH\u20101 with miR\u2010135b r = \u22120.510, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). Total blood tubule density was increased when CircCDR1as was silenced compared with NC (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01 <jats:italic>vs<\/jats:italic>. NC). The number of migrated BMECs were significantly increased in CircCDR1as silencing group compared with NC group (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05 <jats:italic>vs<\/jats:italic>. NC). In addition, CircCDR1as plasmids transfection increased the protein expressions of FIH\u20101 (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05 <jats:italic>vs<\/jats:italic>. NC) and reduced the HIF\u20101\u03b1 as well as VEGF expression compared with NC group (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05 <jats:italic>vs<\/jats:italic>. NC). FISH, RNA pull down, RIP, and luciferase assay identified that FIH\u20101 was a target of miR\u2010135b and could be modulated by CircCDR1as.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>CircCDR1as decreases angiogenesis and proliferation of BMECs by sponging miR\u2010135b and upregulate FIH\u20101.<\/jats:p><\/jats:sec>","DOI":"10.1111\/os.12883","type":"journal-article","created":{"date-parts":[[2021,2,23]],"date-time":"2021-02-23T06:59:12Z","timestamp":1614063552000},"page":"573-582","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["<scp>CircCDR1as<\/scp> Suppresses Bone Microvascular Endothelial Cell Activity and Angiogenesis Through Targeting <scp>miR<\/scp>\u2010135b\/ <scp>FIH<\/scp>\u20101 Axis"],"prefix":"10.1111","volume":"13","author":[{"given":"Zheng","family":"Mao","sequence":"first","affiliation":[{"name":"Department of Rehabilitation, The third Affiliated Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, The third Affiliated Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gui\u2010Yang","family":"Xiao","sequence":"additional","affiliation":[{"name":"Home for the Aged Guangzhou  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of orthopedics, The Third affiliated hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8678-2012","authenticated-orcid":false,"given":"Yu\u2010Cong","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, The third Affiliated Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,2,22]]},"reference":[{"key":"e_1_2_5_2_1","first-page":"15","article-title":"Histopathological aspects and staging systems in non\u2010traumatic femoral head osteonecrosis: an overview of the literature","volume":"87","author":"Benedetto P","year":"2016","journal-title":"Acta Bio\u2010Medica"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.4103\/0366-6999.168017"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003086-199701000-00006"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/10623320600904211"},{"key":"e_1_2_5_6_1","first-page":"51","article-title":"Epidemiology of traumatic and nontraumatic osteonecrosis","volume":"130","author":"Jacobs B","year":"1978","journal-title":"Clin Orthop Relat 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