{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:56:35Z","timestamp":1790636195727,"version":"4.1.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011789","name":"Department of Science and Technology of Jilin Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011789","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Steroid-induced osteonecrosis of the femoral head (SONFH) is characterized by disrupted osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). The long noncoding RNA HOTAIR is aberrantly upregulated in SONFH-BMSCs, yet its functional role in the differentiation imbalance remains incompletely understood. In this study, we investigated whether HOTAIR silencing could restore the differentiation balance in SONFH-BMSCs and clarify the underlying regulatory mechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>HOTAIR was knocked down in SONFH-BMSCs using small interfering RNA (si-HOTAIR). Osteogenic differentiation was assessed using alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining, while adipogenic differentiation was evaluated using Oil Red O staining. Expression of lineage-specific markers and Wnt pathway components was measured using qRT-PCR and Western blotting. The interactions among HOTAIR, miR-217, and DKK1 were validated through dual-luciferase reporter and rescue experiments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>HOTAIR silencing significantly enhanced osteogenic differentiation, as evidenced by increased ALP activity, mineralization, and upregulation of RUNX2, BMP2, and Osterix, while concurrently suppressing adipogenic differentiation, with reduced lipid droplet formation and downregulation of PPAR\u03b3, C\/EBP\u03b1, and Adipsin. Mechanistically, HOTAIR acted as a candidate competing endogenous RNA (ceRNA) by sponging miR-217, thereby relieving miR-217-mediated repression of DKK1 and inhibiting Wnt\/\u03b2-catenin signaling. HOTAIR knockdown restored miR-217 availability, decreased DKK1 expression, and enhanced \u03b2-catenin expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>HOTAIR inhibition rebalances osteogenic and adipogenic differentiation of SONFH-BMSCs via the miR-217\/DKK1\/Wnt\/\u03b2-catenin axis. These findings identify HOTAIR as an important molecular regulator of BMSC fate determination and provide mechanistic insights into ceRNA-mediated regulation in SONFH pathogenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2026.1917162","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:10:20Z","timestamp":1790633420000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["HOTAIR regulates osteogenic\u2013adipogenic differentiation imbalance through the miR-217\/DKK1-mediated Wnt\/\u03b2-catenin pathway in SONFH-BMSCs"],"prefix":"10.3389","volume":"17","author":[{"given":"Min","family":"Yi","sequence":"first","affiliation":[{"name":"Department of Orthopedics, The Second Hospital of Jilin University, Jilin University","place":["Changchun, Jilin, China"]},{"name":"Joint International Research Laboratory of Aging Active Strategy and Bionic Health in Northeast Asia of Ministry of Education, Jilin University","place":["Changchun, Jilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feifei","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The Second Hospital of Jilin University, Jilin University","place":["Changchun, Jilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenwu","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The Second Hospital of Jilin University, Jilin University","place":["Changchun, Jilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The Second Hospital of Jilin University, Jilin University","place":["Changchun, Jilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"10926","DOI":"10.1002\/jcp.27918","article-title":"The prognostic potential of long noncoding RNA HOTAIR expression in human digestive system carcinomas: a meta-analysis","volume":"234","author":"Abdeahad","year":"2019","journal-title":"J. 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