{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:15:36Z","timestamp":1785417336892,"version":"3.56.0"},"reference-count":47,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["52037007"],"award-info":[{"award-number":["52037007"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["52037007"],"award-info":[{"award-number":["52037007"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Unloading-induced bone loss is a major medical challenge during long-duration human spaceflight, largely driven by suppressed osteoblast-mediated bone formation, and practical countermeasures are needed. Electromagnetic stimulation has shown benefits for bone repair, and its non-invasiveness supports potential space use; however, its single-modality efficacy remains limited. Here, we investigated a combined electromagnetic field (CEMF) integrating a static magnetic field (SMF, 0.4\u20130.6 T) and a pulsed electromagnetic field (PEMF, 0.38 \u00b1 0.19 mT) to attenuate unloading-related bone loss and examine field-induced mechanical stimulation. Finite-element simulations mapped magnetic flux density, field gradient, induced current density, and Lorentz force density in bone tissue. CEMF was evaluated in vivo in hindlimb unloading (HLU) mice and in vitro in MC3T3-E1 osteoblasts. CEMF improved bone mineral density, trabecular and cortical microarchitecture, and mechanical properties in HLU mice, with increased osteoblast number and mineral apposition rate. In vitro, CEMF promoted osteogenic differentiation and upregulated COL1A1 and RUNX2. Transcriptome analysis suggested activation of ECM\u2013integrin mechanical signaling and the PI3K\u2013AKT pathway. These findings indicate that CEMF-induced multiphysics stimulation enhances osteogenic responses and may serve as a complementary, non-invasive countermeasure for spaceflight-associated bone loss.<\/jats:p>","DOI":"10.3390\/cells15131138","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T17:11:49Z","timestamp":1782234709000},"page":"1138","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Combined Electromagnetic Fields Mitigate Unloading-Induced Bone Loss by Enhancing Osteogenic Responses via Multiphysics-Induced Mechanotransduction"],"prefix":"10.3390","volume":"15","author":[{"given":"Chao","family":"Cai","sequence":"first","affiliation":[{"name":"Research & Development Institute in Shenzhen, Northwestern Polytechnical University, Shenzhen 518057, China"},{"name":"School of Life Science and Technology, Northwestern Polytechnical University, Xi\u2019an 710129, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenghang","family":"Wang","sequence":"additional","affiliation":[{"name":"Research & Development Institute in Shenzhen, Northwestern Polytechnical University, Shenzhen 518057, China"},{"name":"Shandong Key Laboratory of Neurorehabilitation, Shandong Engineering Research Center of Precision Intervention for Aging, School of Life Sciences and Health, University of Health and Rehabilitation Sciences, Qingdao 266113, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyu","family":"Liu","sequence":"additional","affiliation":[{"name":"Research & Development Institute in Shenzhen, Northwestern Polytechnical University, Shenzhen 518057, China"},{"name":"School of Life Science and Technology, Northwestern Polytechnical University, Xi\u2019an 710129, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7972-6791","authenticated-orcid":false,"given":"Mengxuan","family":"Zheng","sequence":"additional","affiliation":[{"name":"College of Information Science and Engineering, Northeastern University, Shenyang 110819, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihao","family":"Ren","sequence":"additional","affiliation":[{"name":"Research & Development Institute in Shenzhen, Northwestern Polytechnical University, Shenzhen 518057, China"},{"name":"School of Life Science and Technology, Northwestern Polytechnical University, Xi\u2019an 710129, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengyi","family":"Xue","sequence":"additional","affiliation":[{"name":"Research & Development Institute in Shenzhen, Northwestern Polytechnical University, Shenzhen 518057, China"},{"name":"School of Life Science and Technology, Northwestern Polytechnical University, Xi\u2019an 710129, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Research & Development Institute in Shenzhen, Northwestern Polytechnical University, Shenzhen 518057, China"},{"name":"School of Life Science and Technology, Northwestern Polytechnical University, Xi\u2019an 710129, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zong","sequence":"additional","affiliation":[{"name":"Research & Development Institute in Shenzhen, Northwestern Polytechnical University, Shenzhen 518057, China"},{"name":"School of Life Science and Technology, Northwestern Polytechnical University, Xi\u2019an 710129, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0008-9036","authenticated-orcid":false,"given":"Jiancheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Osteoporosis, Honghui Hospital, Xi\u2019an Jiaotong University, Xi\u2019an 710054, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weikang","family":"Sun","sequence":"additional","affiliation":[{"name":"Research & Development Institute in Shenzhen, Northwestern Polytechnical University, Shenzhen 518057, China"},{"name":"School of Life Science and Technology, Northwestern Polytechnical University, Xi\u2019an 710129, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihua","family":"Li","sequence":"additional","affiliation":[{"name":"Research & Development Institute in Shenzhen, Northwestern Polytechnical University, Shenzhen 518057, China"},{"name":"School of Life Science and Technology, Northwestern Polytechnical University, Xi\u2019an 710129, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tinghua","family":"He","sequence":"additional","affiliation":[{"name":"Research & Development Institute in Shenzhen, Northwestern Polytechnical University, Shenzhen 518057, China"},{"name":"School of Life Science and Technology, Northwestern Polytechnical University, Xi\u2019an 710129, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9197-1421","authenticated-orcid":false,"given":"Xiaotong","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Electrical Engineering, Zhejiang University, Hangzhou 310027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5418-6240","authenticated-orcid":false,"given":"Peng","family":"Shang","sequence":"additional","affiliation":[{"name":"Research & Development Institute in Shenzhen, Northwestern Polytechnical University, Shenzhen 518057, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1359\/JBMR.040307","article-title":"Cortical and trabecular bone mineral loss from the spine and hip in long-duration spaceflight","volume":"19","author":"Lang","year":"2004","journal-title":"J. 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