{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T21:57:29Z","timestamp":1785794249901,"version":"3.56.0"},"reference-count":45,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T00:00:00Z","timestamp":1728518400000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["P30 AR074992"],"award-info":[{"award-number":["P30 AR074992"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000097","name":"National Center for Research Resources","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1 TR000448"],"award-info":[{"award-number":["UL1 TR000448"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P41 GM103422"],"award-info":[{"award-number":["P41 GM103422"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Extracellular Vesicle"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Adult T cell leukaemia (ATL), caused by infection with human T\u2010 lymphotropic virus type 1 (HTLV\u20101), is often complicated by hypercalcemia and osteolytic lesions. Therefore, we studied the communication between patient\u2010derived ATL cells (ATL\u2010PDX) and HTLV\u20101 immortalized CD4+ T cell lines (HTLV\/T) with osteoclasts and their effects on bone mass in mice. Intratibial inoculation of some HTLV\/T leads to a profound local decrease in bone mass similar to marrow\u2010replacing ATL\u2010PDX, despite the fact that few HTLV\/T cells persisted in the bone. To study the direct effect of HTLV\/T and ATL\u2010PDX on osteoclasts, supernatants were added to murine and human osteoclast precursors. ATL\u2010PDX supernatants from hypercalcemic patients promoted the formation of mature osteoclasts, while those from HTLV\/T were variably stimulatory, but had largely consistent effects between human and murine cultures. Interestingly, this osteoclastic activity did not correlate with expression of osteoclastogenic cytokine receptor activator of nuclear factor kappa\u2010B ligand (RANKL), suggesting an alternative mechanism. HTLV\/T and ATL\u2010PDX produce small extracellular vesicles (sEV), known to facilitate HTLV\u20101 infection. We hypothesized that these sEV also mediate bone loss by targeting osteoclasts. We isolated sEV from both HTLV\/T and ATL\u2010PDX, and found they carried most of the activity found in supernatants. In contrast, sEV from uninfected activated T cells had little effect. Analysis of sEV (both active and inactive) by mass spectrometry and electron microscopy confirmed absence of RANKL and intact virus. Viral proteins Tax and Env were only present in sEV from the active, osteoclast\u2010stimulatory group, along with increased representation of proteins involved in osteoclastogenesis and bone resorption. sEV from osteoclast\u2010active HTLV\/T injected over mouse calvaria in the presence of low\u2010dose RANKL caused more osteolysis than osteoclast\u2010inactive sEV or RANKL alone. Thus, HTLV\u20101 infection of T cells can cause release of sEV with strong osteolytic potential, providing a mechanism beyond RANKL production that modifies the bone microenvironment, even in the absence of overt leukaemia.<\/jats:p>","DOI":"10.1002\/jev2.12516","type":"journal-article","created":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T08:39:34Z","timestamp":1728549574000},"source":"Crossref","is-referenced-by-count":5,"title":["HTLV\u20101 infected T cells cause bone loss via small extracellular vesicles"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1538-2019","authenticated-orcid":false,"given":"Nitin Kumar","family":"Pokhrel","sequence":"first","affiliation":[{"name":"Division of Bone &amp; Mineral Diseases, Musculoskeletal Research Center Washington University School of Medicine  Saint Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda 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