{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T12:10:28Z","timestamp":1789906228119,"version":"4.0.1"},"reference-count":78,"publisher":"The Endocrine Society","issue":"11","license":[{"start":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T00:00:00Z","timestamp":1660694400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81960392"],"award-info":[{"award-number":["81960392"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82060169"],"award-info":[{"award-number":["82060169"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,10,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Idiopathic short stature (ISS), a disorder of unknown cause, accounts for approximately 80% of the clinical diagnoses of children with short stature. Exosomal circular RNA in plasma has been implicated in various disease processes. However, the role of exosome-derived circRNA in ISS has not been elucidated yet.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Plasma exosomes of ISS and normal children were cocultured with human chondrocytes. Microarray analysis and RT-PCR identified the differential expression of circRNA in exosomes between ISS and normal children. Hsa_circ_0063476 was upregulated or downregulated in human chondrocytes. Subsequently, overexpression rats of hsa_circ_0063476 was constructed via adenoviral vector to further validate the role of hsa_circ_0063476 on longitudinal bone growth via in vivo experiment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The plasma exosome of ISS children suppressed the expression of markers of chondrocyte hypertrophy and endochondral ossification. Subsequently, upregulation of hsa_circ_0063476 in ISS exosome was identified. In vitro experiments demonstrated that chondrocyte proliferation, cell cycle and endochondral ossification were suppressed, and apoptosis was increased following hsa_circ_0063476 overexpression in human chondrocytes. Conversely, silencing hsa_circ_0063476 in human chondrocytes can show opposite outcomes. Our study further revealed hsa_circ_0063476 overexpression in vitro can enhance chondrocyte apoptosis and inhibit the expression of markers of chondrocyte proliferation and endochondral ossification via miR-518c-3p\/DDX6 axis. Additionally, the rats with hsa_circ_0063476 overexpression showed a short stature phenotype.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The authors identified a novel pathogenesis in ISS that exosome-derived hsa_circ_0063476 retards the expression of markers of endochondral ossification and impairs longitudinal bone growth via miR-518c-3p\/DDX6 axis, which may provide a unique therapeutic avenue for ISS.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/endocr\/bqac138","type":"journal-article","created":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T04:17:07Z","timestamp":1660709827000},"source":"Crossref","is-referenced-by-count":3,"title":["Circulating Exosomal circRNA_0063476 Impairs Expression of Markers of Bone Growth Via the miR-518c-3p\/DDX6 Axis in ISS"],"prefix":"10.1210","volume":"163","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8704-3868","authenticated-orcid":false,"given":"Zhi","family":"Du","sequence":"first","affiliation":[{"name":"Departments of Orthopedics, The Second Affiliated Hospital of Nanchang University , Nanchang City, Jiangxi Province , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghong","family":"Yuan","sequence":"additional","affiliation":[{"name":"Departments of Orthopedics, The Second Affiliated Hospital of Nanchang University , Nanchang City, Jiangxi Province , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwen","family":"Wu","sequence":"additional","affiliation":[{"name":"Departments of Orthopedics, The Second Affiliated Hospital of Nanchang University , Nanchang City, Jiangxi Province , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynecology, The First Affiliated Hospital of Nanchang University , Nanchang City, Jiangxi Province , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7302-9643","authenticated-orcid":false,"given":"Xijuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Second Affiliated Hospital of Nanchang University , Nanchang City, Jiangxi Province , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7128-2621","authenticated-orcid":false,"given":"Jingyu","family":"Jia","sequence":"additional","affiliation":[{"name":"Departments of Orthopedics, The Second Affiliated Hospital of Nanchang University , Nanchang City, Jiangxi Province , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2022,8,17]]},"reference":[{"issue":"Suppl 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