{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T19:05:16Z","timestamp":1785870316287,"version":"3.56.0"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T00:00:00Z","timestamp":1767052800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T00:00:00Z","timestamp":1767052800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Impaired osteogenic differentiation serves as a pivotal pathogenic mechanism underlying osteonecrosis of the femoral head (ONFH). This study systematically investigated the pro\u2010osteogenic effects of exosomal miR\u20104787\u20103p derived from bone marrow mesenchymal stem cells (BMSCs) in the pathogenesis of ONFH. Bone marrow was collected from both healthy donors and patients with post\u2010traumatic ONFH. BMSC and BMSC\u2010derived exosomes were isolated and characterized. BMSCs were transfected with miR\u20104787\u20103p mimic and inhibitor to collect exosomes. These exosomes were used to treat BMSCs stimulated by dexamethasone (DEX). A dual luciferase reporter gene assay was employed to verify the binding of miR\u20104787\u20103p and programmed cell death 4 (PDCD4). BMSCs were transfected with PDCD4 shRNA and stimulated by DEX. BMSCs transfected by PDCD4 vectors were stimulated by exosomes and DEX. Cell counting kit\u20108 assay, Alizarin red staining, and ALP activity detection were performed on BMSCs. Molecular analyses included qRT\u2010PCR and Western blot of osteogenic markers and PDCD4 signaling components. BMSC and BMSC\u2010derived exosomes were successfully isolated. Relative to healthy donors, miR\u20104787\u20103p was downregulated in BMSC\u2010derived exosomes from patients with traumatic ONFH. Exosomal miR\u20104787\u20103p enhanced BMSCs' viability and osteogenic differentiation, as evidenced by increased mineralization, ALP activity, and upregulation of ALP\/OPN\/Runx2. PDCD4 was a target of miR\u20104787\u20103p. PDCD4 was up\u2010modulated in BMSCs from patients with traumatic ONFH. PDCD4 knockdown enhanced BMSCs' viability, Alizarin red staining, ALP activity, ALP, OPN and Runx2 expression. PDCD4 reversed BMSC\u2010derived exosomal miR\u20104787\u20103p promotion on BMSCs' viability, Alizarin red staining, ALP activity, ALP, OPN and Runx2 expression. BMSC\u2010derived exosomal miR\u20104787\u20103p promoted BMSCs' osteogenic differentiation through direct targeting of PDCD4. These findings suggest its potential therapeutic application for ONFH by reversing impaired osteogenesis.<\/jats:p>","DOI":"10.1002\/jbt.70662","type":"journal-article","created":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T17:28:38Z","timestamp":1767115718000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Bone Marrow Mesenchymal Stem Cell\u2010Derived Exosomal miR\u20104787\u20103p Promoted Osteogenic Differentiation by Targeting PDCD4 in Osteonecrosis of Femoral Head"],"prefix":"10.1002","volume":"40","author":[{"given":"Peiyan","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery Shanghai Fifth People's Hospital Affiliated to Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangda","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Shanghai Fifth People's Hospital Affiliated to Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingfeng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Shanghai Fifth People's Hospital Affiliated to Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3170-7012","authenticated-orcid":false,"given":"Jun","family":"He","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Shanghai Fifth People's Hospital Affiliated to Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Shanghai Fifth People's Hospital Affiliated to Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4713-5482","authenticated-orcid":false,"given":"Yueming","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Shanghai Fifth People's Hospital Affiliated to Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,30]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13018-019-1359-7"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/7126982"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/8140595"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reth.2020.11.003"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/2211-5463.13037"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.2147\/ORR.S281030"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-2496-y"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00590-012-1161-2"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2017.12.010"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S178698"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.12418"},{"issue":"22","key":"e_1_2_12_13_1","article-title":"MiR\u2010146a Regulates Osteogenic Differentiation and Proliferation of Bone Marrow Stromal Cells in Traumatic Femoral Head Necrosis","volume":"24","author":"Kong Y.","year":"2020","journal-title":"European Review for Medical and Pharmacological Sciences"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13018-020-01688-5"},{"issue":"22","key":"e_1_2_12_15_1","first-page":"9761","article-title":"MiR\u201015b Ameliorates Sonfh by Targeting Smad7 and Inhibiting Osteogenic Differentiation of BMSCs","volume":"23","author":"Fang S. 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