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However, current non-surgical treatment for OA can only relieve pain without obvious cartilage and subchondral bone repair. Mesenchymal stem cell (MSC)-secreted exosomes have promising therapeutic effects on knee OA, but the efficacy of MSC-exosome therapy is not well determined, and the mechanisms involved are still unclear. In this study, we isolated dental pulp stem cell (DPSC)-derived exosomes by ultracentrifugation and determined the therapeutic effects of a single intra-articular injection of DPSC-derived exosomes in a mice knee OA model. The results showed that the DPSC-derived exosomes effectively improved abnormal subchondral bone remodeling, inhibited the occurrence of bone sclerosis and osteophytes, and alleviated cartilage degradation and synovial inflammation in vivo. Moreover, transient receptor potential vanilloid 4 (TRPV4) was activated during the progression of OA. Enhanced TRPV4 activation facilitated osteoclast differentiation, and TRPV4 inhibition blocked this process in vitro. DPSC-derived exosomes repressed osteoclast activation in vivo by inhibiting TRPV4 activation. Our findings demonstrated that a topical, single injection of DPSC-derived exosomes is a potential strategy for knee OA treatment, and that the exosomes regulated osteoclast activation by TRPV4 inhibition, which may act as a promising target for clinical OA treatment.<\/jats:p>","DOI":"10.3390\/ijms24054926","type":"journal-article","created":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T03:49:08Z","timestamp":1678074548000},"page":"4926","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Dental Pulp Stem Cell-Derived Exosomes Alleviate Mice Knee Osteoarthritis by Inhibiting TRPV4-Mediated Osteoclast Activation"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9792-4749","authenticated-orcid":false,"given":"Yu","family":"Fu","sequence":"first","affiliation":[{"name":"Fourth Clinical Division, Peking University School and Hospital of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengjie","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, Peking University School and Hospital of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanheng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, Peking University School and Hospital of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixin","family":"Qiu","sequence":"additional","affiliation":[{"name":"Fourth Clinical Division, Peking University School and Hospital of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16214","DOI":"10.1038\/s41598-017-15376-8","article-title":"Mesenchymal stem cells derived exosomes and microparticles protect cartilage and bone from degradation in osteoarthritis","volume":"7","author":"Cosenza","year":"2017","journal-title":"Sci. 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