{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T06:23:02Z","timestamp":1770963782870,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,5,4]],"date-time":"2020-05-04T00:00:00Z","timestamp":1588550400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["8167140951"],"award-info":[{"award-number":["8167140951"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Orthopaedic Surgery"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Nontraumatic osteonecrosis of the femoral head (ONFH) is one of the most common diseases in orthopaedics. The damage to vascular endothelial (VE) cells caused by glucocorticoids (GC) has been reported as a possible mechanism of pathogenesis for ONFH. Junction\u2010mediating and regulatory protein (JMY), originally identified as a p53 coactivator, plays prominent roles in the DNA damage response and in cell motility. This study aimed to discover the role of JMY in the pathogenesis of GC\u2010induced endothelial cell lesions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>High\u2010throughput RNA sequencing was performed to identify the differentially expressed genes between GC\u2010treated human umbilical vein endothelial cells (HUVEC) and control cells. JMY knockdown and overexpressing HUVEC lines were treated with GC. Cell proliferation was examined with a survival cell count assay (Cell Counting Kit\u20108, CCK\u20108); cell apoptosis was measured by flow cytometry; a scarification assay was used to detect the capability of cell migration; a Transwell chamber assay was done to detect the cell motility . Differential expression of cell protein was detected by western blot.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 1561 differential genes were obtained through transcription sequencing, of which 789 mRNA were upregulated and 772 mRNA were downregulated in the GC\u2010treated HUVEC compared with the control cells. CCK\u20108 assay results showed that: without GC treatment, overexpression or knockdown of JMY did not affect the proliferation activity of HUVEC. In the presence of GC treatment, the proliferation activity of HUVEC in the JMY knockdown group was significantly higher than that in the control group (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01). The proliferation activity of HUVEC in the overexpression JMY group was significantly lower than that in the control group (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01). The results of flow cytometry showed that without GC treatment, overexpression or knockdown of JMY did not affect the apoptosis proportion of HUVEC. With GC treatment, the apoptosis proportion of HUVEC in the JMY knockdown group was significantly lower than that in the control group (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01), and the apoptosis proportion of HUVEC in the overexpression JMY group was significantly higher than that in the control group (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01). Western blot results showed that with GC treatment, the JMY expression level of HUVEC increased with the reaction time. Moreover, the distribution of JMY was mainly concentrated in the nucleus. The expression level of Bax also increased with the reaction time. With GC treatment, overexpression of JMY could significantly increase the expression of Bax in HUVEC. JMY knockdown could reduce the expression of Bax in HUVEC. In the absence of GC treatment, HUVEC overexpression or knockdown of JMY did not affect the expression of Bax. The results of scarification and Transwell chamber assays showed that: without GC treatment, JMY knockdown could significantly decrease the cell motility and increase the expression level of VE\u2010cadherin in HUVEC; with GC treatment, JMY knockdown in HUVEC had lower cell motility compared with the control group (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Glucocorticoids can induce the HUVEC apoptosis, and reduce its proliferation, cell motility. Our results mainly confirmed the role of JMY in the pathogenesis of GC\u2010inducing lesions in HUVEC. GC act on HUVEC, inducing cell damage. Following the event of cell damage, JMY levels upregulate in the nucleus to induce transcription of Bax, triggering apoptosis. JMY can also regulate HUVEC motility <jats:italic>via<\/jats:italic> its regulation of VE\u2010cadherin levels.<\/jats:p><\/jats:sec>","DOI":"10.1111\/os.12680","type":"journal-article","created":{"date-parts":[[2020,5,4]],"date-time":"2020-05-04T07:30:36Z","timestamp":1588577436000},"page":"964-973","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Role of Junction\u2010Mediating and Regulatory Protein in the Pathogenesis of Glucocorticoid\u2010Induced Endothelial Cell Lesions"],"prefix":"10.1111","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1483-1302","authenticated-orcid":false,"given":"Wei","family":"Zuo","sequence":"first","affiliation":[{"name":"Peking University China\u2013Japan Friendship School of Clinical Medicine  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wan\u2010shou","family":"Guo","sequence":"additional","affiliation":[{"name":"Peking University China\u2013Japan Friendship School of Clinical Medicine  Beijing China"},{"name":"Department of Orthopaedic Surgery, Center for Osteonecrosis and Joint Preserving &amp; Reconstruction China\u2010Japan Friendship Hospital  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua\u2010chen","family":"Yu","sequence":"additional","affiliation":[{"name":"Graduate School of Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei","family":"Liu","sequence":"additional","affiliation":[{"name":"Beijing University of Chinese Medicine  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi\u2010dong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Center for Osteonecrosis and Joint Preserving &amp; Reconstruction China\u2010Japan Friendship Hospital  Beijing 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