{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T06:06:54Z","timestamp":1789020414385,"version":"build-2803163510"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"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. Cell Dev. Biol."],"abstract":"<jats:p>Extracellular vesicles (EVs) are membrane-bound vesicles that regulate intercellular signaling by transporting cellular cargo including RNAs, proteins, and lipids. In recent years, EVs have emerged as promising biologic therapeutics for musculoskeletal repair, recapitulating many of the benefits of mesenchymal stromal cells. However, strategies to enhance the therapeutic potential of EVs remains limited. Here, we investigated how cyclic mechanical strain influences the microRNA (miRNA) cargo and function of EVs produced by primary C57BL\/6 murine myogenic cells. Specifically, we aimed to determine how biomechanical strain regimens alter myogenic EV cargo and regulate the transcriptome of recipient myoblasts. We identified miR-222 as a miRNA that was significantly and selectively enriched in low-strain long-duration (LSLD) mechanically strained EVs compared to Static EVs and to high-strain short-duration (HSSD) EVs. Recipient primary myoblasts treated with LSLD EVs displayed distinct transcriptomic changes, characterized by a statistically significant overrepresentation of downregulated predicted target genes associated with miR-222\u20135p and miR-222\u20133p at 24\u00a0h and 72\u00a0h after LSLD EV treatment, respectively. This transcriptomic shift correlated with an increase in Myosin Heavy Chain (MyHC) expression in recipient myoblasts. Together, these findings demonstrate that biomechanical strain regulates the packaging of miRNAs within myogenic EVs, and that LSLD EV delivery is associated with a differentiation-related phenotype in recipient myoblasts. This work provides a foundation for future studies utilizing biomechanical cues to tune EV cargo for potential therapeutic applications in muscle repair and regeneration.<\/jats:p>","DOI":"10.3389\/fcell.2026.1858881","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:31:22Z","timestamp":1789018282000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Biomechanical strain alters the microRNA cargo of primary myogenic cell-derived extracellular vesicles associated with a differentiation phenotype"],"prefix":"10.3389","volume":"14","author":[{"given":"Katherine B.","family":"Williams","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University","place":["Fort Collins, CO, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Chubb","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University","place":["Fort Collins, CO, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelby","family":"Osburn","sequence":"additional","affiliation":[{"name":"Department of Health and Exercise Science, College of Health and Human Sciences, Colorado State University","place":["Fort Collins, CO, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Health and Exercise Science, College of Health and Human Sciences, Colorado State University","place":["Fort Collins, CO, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley","family":"Guilliams","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Natural Sciences, Colorado State University","place":["Fort Collins, CO, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melinda","family":"Meyers","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University","place":["Fort Collins, CO, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"LaRocca","sequence":"additional","affiliation":[{"name":"Department of Health and Exercise Science, College of Health and Human Sciences, Colorado State University","place":["Fort Collins, CO, United States"]},{"name":"Center for Healthy Aging, Colorado State University","place":["Fort Collins, CO, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karyn L.","family":"Hamilton","sequence":"additional","affiliation":[{"name":"Department of Health and Exercise Science, College of Health and Human Sciences, Colorado State University","place":["Fort Collins, CO, United States"]},{"name":"Center for Healthy Aging, Colorado State University","place":["Fort Collins, CO, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Ehrhart","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University","place":["Fort Collins, CO, United States"]},{"name":"Center for Healthy Aging, Colorado State University","place":["Fort Collins, CO, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1089\/ten.tea.2009.0113","article-title":"The synergistic effect of treadmill running on stem-cell transplantation to heal injured skeletal muscle","volume":"16","author":"Ambrosio","year":"2010","journal-title":"Tissue Eng. 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