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periodontitis (CAP) is a disease with characteristics of inflammation and bone loss. In this study, our objective was to examine the function of small extracellular vesicles (sEVs) obtained from milk in encouraging osteogenic differentiation and inhibiting inflammation by miR-21 in CAP. The expression of miR-21 was detected using qRT-PCR in human CAP samples. The impact of miR-21 on the process of osteogenic differentiation was investigated using CCK-8, qRT-PCR, immunofluorescence staining, and Western blot analysis. The evaluation of RAW 264.7 cell polarization and the assessment of inflammatory factor expression were conducted through qRT-PCR. The influence of sEVs on MC3T3-E1 cells and RAW 264.7 cells was examined, with a particular emphasis on the involvement of miR-21. In human CAP samples, a decrease in miR-21 expression was observed. MiR-21 increased the expression of osteogenesis-related genes and M2 polarization genes while decreasing the expression of M1 polarization genes and inflammatory cytokines. Treatment with milk-derived sEVs also promoted osteogenesis and M2 polarization while inhibiting M1 polarization and inflammation. Conversely, the addition of miR-21 inhibitors resulted in opposite effects. Our results indicated that sEVs derived from milk had a positive effect on bone formation and activation of anti-inflammatory (M2) macrophages and simultaneously reduced inflammation by regulating miR-21 in CAP.<\/jats:p>","DOI":"10.3390\/ijms241813873","type":"journal-article","created":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T09:00:52Z","timestamp":1694422852000},"page":"13873","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Milk-Derived Small Extracellular Vesicles Promote Osteogenic Differentiation and Inhibit Inflammation via microRNA-21"],"prefix":"10.3390","volume":"24","author":[{"given":"Runyuan","family":"Liu","sequence":"first","affiliation":[{"name":"School of Stomatology, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Stomatology, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5717-4296","authenticated-orcid":false,"given":"Saixuan","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Stomatology, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Xia","sequence":"additional","affiliation":[{"name":"School of Stomatology, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanqing","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Stomatology, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Stomatology, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Dong","sequence":"additional","affiliation":[{"name":"School of Stomatology, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidong","family":"Niu","sequence":"additional","affiliation":[{"name":"School of Stomatology, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"908859","DOI":"10.3389\/fcimb.2022.908859","article-title":"Mechanisms of bone remodeling and therapeutic strategies in chronic apical periodontitis","volume":"12","author":"Luo","year":"2022","journal-title":"Front. 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