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Matrix-bound nanovesicles (MBVs) are a subclass of extracellular vesicle recently shown to mitigate inflammation in preclinical models of rheumatoid arthritis and influenza-mediated \u201ccytokine storm.\u201d The molecular mechanism of these anti-inflammatory properties is only partially understood. The objective of the present study was to investigate the effects of MBV on RANKL-induced osteoclast formation in vitro and particulate-induced osteolysis in vivo. Results showed that MBV attenuated osteoclast differentiation and activity by suppressing the NF-\u03baB signaling pathway and downstream NFATc1, DC-STAMP, c-Src, and cathepsin K expression. In vivo, local administration of MBV attenuated ultrahigh molecular weight polyethylene particle-induced osteolysis, bone reconstruction, and periosteal inflammation. The results suggest that MBV may be a therapeutic option for preventing periprosthetic loosening.<\/jats:p>","DOI":"10.1126\/sciadv.adn1852","type":"journal-article","created":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T18:00:56Z","timestamp":1729274456000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":25,"title":["Matrix-bound nanovesicles alleviate particulate-induced periprosthetic osteolysis"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4421-0390","authenticated-orcid":true,"given":"Runzhi","family":"Liao","sequence":"first","affiliation":[{"name":"McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA."},{"name":"Xiangya Hospital, Central South University, Changsha, Hunan 410008, China."},{"name":"Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6074-7139","authenticated-orcid":true,"given":"Marley J.","family":"Dewey","sequence":"additional","affiliation":[{"name":"McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA."},{"name":"Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0713-8583","authenticated-orcid":true,"given":"Jiayang","family":"Rong","sequence":"additional","affiliation":[{"name":"McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0164-6802","authenticated-orcid":true,"given":"Scott A.","family":"Johnson","sequence":"additional","affiliation":[{"name":"McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6778-6816","authenticated-orcid":true,"given":"William A.","family":"D\u2019Angelo","sequence":"additional","affiliation":[{"name":"McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5636-0994","authenticated-orcid":true,"given":"George S.","family":"Hussey","sequence":"additional","affiliation":[{"name":"McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA."},{"name":"Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3555-0689","authenticated-orcid":true,"given":"Stephen F.","family":"Badylak","sequence":"additional","affiliation":[{"name":"McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA."},{"name":"Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA."},{"name":"Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15219, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.17.01617"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1302\/0301-620X.93B3.25467"},{"key":"e_1_3_2_4_2","first-page":"99","article-title":"Wear particles","volume":"88","author":"Jacobs J. 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