{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:10:43Z","timestamp":1787026243367,"version":"build-2736575974"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:00:00Z","timestamp":1759968000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioeng. Biotechnol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Osteonecrosis of the femoral head (ONFH) is a refractory orthopedic disease in which steroids may induce bone cell necroptosis. Extracellular vesicles derived from bone marrow mesenchymal stromal cells (BMSC-EVs) are recognized as novel therapies to improve ONFH. Pulsed electromagnetic fields (PEMFs) increase the paracrine activity of BMSCs. Nonetheless, the effect and mechanism of PEMFs preconditioned BMSC-EVs (BMSC-EVs\n                      <jats:sup>PEMFs<\/jats:sup>\n                      ) for treating ONFH are unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The BMSC-EVs\n                      <jats:sup>PEMFs<\/jats:sup>\n                      with different magnetic amplitudes were incubated with dexamethasone-induced MC3T3-E1 cells and the osteogenic differentiation and necroptosis were observed. Furthermore, RNA sequencing of MC3T3-E1 cells incubated with incubated with PEMFs of a specific amplitude or without PEMFs was conducted to identify potential mechanisms involved. Reverse transcription\u2012quantitative polymerase chain reaction (RT-qPCR), immunofluorescence and Western blotting were performed to detect necroptosis-related pathways. SD rats receiving steroid injections were randomly assigned to receive PBS, BMSC-EVs or BMSC-EVs\n                      <jats:sup>PEMFs<\/jats:sup>\n                      therapy. Micro-CT scan, histological, and immunohistochemical analyses were used to evaluate the therapeutic effects on bone formation and necroptosis of the femoral head in ONFH animals.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The characteristics of the BMSC-EVs\n                      <jats:sup>PEMFs<\/jats:sup>\n                      were similar to those of the BMSC-EVs.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , co-culture of osteoblasts and PEMFs with 3\u00a0millitesla (mT) amplitude preconditioned BMSC-EVs (BMSC-EVs\n                      <jats:sup>PEMFs (3 mT)<\/jats:sup>\n                      promoted osteogenic differentiation and inhibited cell death. The results of RNA sequencing revealed that the expression of Ripk3 was significantly lower in the BMSC-EVs\n                      <jats:sup>PEMFs (3 mT)<\/jats:sup>\n                      group than in the BMSC-EVs group. RT-qPCR, immunofluorescence and Western blotting revealed that the expression of necroptosis-related molecules (RIPK1, RIPK3, and MLKL) was suppressed in BMSC-EVs\n                      <jats:sup>PEMFs (3 mT)<\/jats:sup>\n                      group (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.05).\n                      <jats:italic>In vivo<\/jats:italic>\n                      , the BMSC-EVs\n                      <jats:sup>PEMFs (3 mT)<\/jats:sup>\n                      group presented better bone morphology of the femoral head via micro-CT, with a lower protein expression of MLKL and a higher expression of RUNX2 (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.05) at 2\u00a0weeks, while lower expressions of RIPK1 and RIPK3, and higher levels of RUNX2 and OCN (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.05) at the femoral head at 6\u00a0weeks after injection than did the BMSCs-EVs group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PEMFs with 3\u00a0mT amplitude preconditioned BMSC-EVs could promote bone formation by inhibiting osteoblasts necroptosis via Ripk1\u2013Ripk3\u2013Mlkl signaling in ONFH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fbioe.2025.1655579","type":"journal-article","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T12:57:53Z","timestamp":1760014673000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Pulsed electromagnetic fields preconditioned extracellular vesicles derived from mesenchymal stromal cells prevents necroptosis of osteoblasts in osteonecrosis of the femoral head rats"],"prefix":"10.3389","volume":"13","author":[{"given":"Xiao-Na","family":"Xiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang-Yin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang-Xiu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Chen","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Qi","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1177\/0022034510378427","article-title":"Osteogenic potential of mandibular vs. long-bone marrow stromal cells","volume":"89","author":"Aghaloo","year":"2010","journal-title":"J. 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