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How different loading intensities alter the biological effect of these vesicles is not fully understood. Dynamic fluid shear stress at low intensity (0.7\u2009\u00b1\u20090.3\u2009Pa, 5\u2009Hz) or high intensity (2.9\u2009\u00b1\u20090.2\u2009Pa, 1\u2009Hz) was used on mouse hematopoietic progenitor cells for 2 min in the presence or absence of chemical compounds that inhibit release or biogenesis of extracellular vesicles. We used a Receptor activator of nuclear factor kappa\u2010\u0392 ligand\u2010induced osteoclastogenesis assay to evaluate the biological effect of different fractions of extracellular vesicles obtained through centrifugation of medium from hematopoietic stem cells. Osteoclast formation was reduced by microvesicles (10\u2009000\u00d7\u2009\n                    <jats:italic>g<\/jats:italic>\n                    ) obtained after low\u2010intensity loading and induced by exosomes (100\u2009000\u00d7\u2009\n                    <jats:italic>g<\/jats:italic>\n                    ) obtained after high\u2010intensity loading. These osteoclast\u2010modulating effects could be diminished or eliminated by depletion of extracellular vesicles from the conditioned medium, inhibition of general extracellular vesicle release, inhibition of microvesicle biogenesis (low intensity), inhibition of ESCRT\u2010independent exosome biogenesis (high intensity), as well as by inhibition of dynamin\u2010dependent vesicle uptake in osteoclast progenitor cells. Taken together, the intensity of mechanical loading affects the release of extracellular vesicles and change their osteoclast\u2010modulating effect.\n                  <\/jats:p>","DOI":"10.1096\/fj.202301520r","type":"journal-article","created":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T11:25:27Z","timestamp":1701170727000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Mechanical loading intensities affect the release of extracellular vesicles from mouse bone marrow\u2010derived hematopoietic progenitor cells and change their osteoclast\u2010modulating effect"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9302-0710","authenticated-orcid":false,"given":"C.","family":"Bratengeier","sequence":"first","affiliation":[{"name":"Department of Biomedical and Clinical Sciences Link\u00f6ping University  Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4493-1478","authenticated-orcid":false,"given":"L.","family":"Johansson","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences Link\u00f6ping University  Link\u00f6ping Sweden"},{"name":"Department of Clinical Pathology Link\u00f6ping University  Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7252-6736","authenticated-orcid":false,"given":"A.","family":"Liszka","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences Link\u00f6ping University  Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0280-9124","authenticated-orcid":false,"given":"A. 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