{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T05:07:19Z","timestamp":1779512839443,"version":"3.53.1"},"reference-count":45,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013142","name":"Key Research and Development Project of Hainan Province","doi-asserted-by":"crossref","award":["2023ICAC YANFA"],"award-info":[{"award-number":["2023ICAC YANFA"]}],"id":[{"id":"10.13039\/501100013142","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100013142","name":"Key Research and Development Project of Hainan Province","doi-asserted-by":"crossref","award":["2024ICAC YANFA"],"award-info":[{"award-number":["2024ICAC YANFA"]}],"id":[{"id":"10.13039\/501100013142","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100013142","name":"Key Research and Development Project of Hainan Province","doi-asserted-by":"crossref","award":["2026ICAC YANFA"],"award-info":[{"award-number":["2026ICAC YANFA"]}],"id":[{"id":"10.13039\/501100013142","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Postmenopausal osteoporosis is associated with cellular senescence and the accumulation of the senescence-associated secretory phenotype (SASP). While mesenchymal stem cell (MSC)-derived exosomes show tissue repair potential, the efficacy and mechanisms of MSC-derived apoptotic vesicles (apoVs) remain unclear. This study compared MSC-apoVs and exosomes in postmenopausal osteoporosis and investigated the underlying epigenetic mechanisms. Methods: Therapeutic efficacy was evaluated in an ovariectomized (OVX) mouse model and senescent human bone marrow mesenchymal stem cells (hBMMSCs). Small RNA sequencing identified differential microRNA (miRNA) cargos between vesicle types. SASP-related cytokine expression (IL-6, TNF-\u03b1, MCP-1) and pathway activation were assessed by RT-qPCR, ELISA, and Western blot. Results: MSC-apoV treatment attenuated bone loss in OVX mice and reduced SASP expression in senescent hBMMSCs to a greater extent than exosomes. Small RNA sequencing revealed that apoVs were enriched with a specific miRNA cluster, including hsa-let-7b-5p, hsa-miR-92a-3p, and hsa-miR-98-5p. Bioinformatic analyses identified BRAF and CRKL as downstream targets of this miRNA cluster, supported by reduced protein levels after apoV treatment. Subsequent molecular assays showed that apoV treatment inhibited the phosphorylation of both the MAPK (p38 and JNK) and NF-\u03baB (p65) signaling pathways, which correlated with reduced local inflammation in the bone marrow microenvironment and preserved osteogenic differentiation capacity. Conclusions: MSC-apoVs attenuate postmenopausal osteoporosis more effectively than exosomes. This enhanced efficacy is associated with the delivery of an enriched miRNA cluster that inhibits MAPK and NF-\u03baB signaling, together with suppression of BRAF and CRKL protein expression. ApoVs may represent a cell-free therapeutic strategy for age-related bone loss.<\/jats:p>","DOI":"10.3390\/ph19050777","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T13:12:08Z","timestamp":1779455528000},"page":"777","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["MSC-Derived Apoptotic Vesicles Restore Bone Marrow Niche Homeostasis in Postmenopausal Osteoporosis by miRNA-Mediated Suppression of MAPK and NF-\u03baB Signaling Nodes"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3834-7629","authenticated-orcid":false,"given":"Zhiwen","family":"Tu","sequence":"first","affiliation":[{"name":"International Center for Aging and Cancer, Hainan Medical University, Haikou 571199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4733-0296","authenticated-orcid":false,"given":"Haolin","family":"Wu","sequence":"additional","affiliation":[{"name":"International Center for Aging and Cancer, Hainan Medical University, Haikou 571199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youxi","family":"Jiang","sequence":"additional","affiliation":[{"name":"Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-Sen University, Guangzhou 510055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7908-6837","authenticated-orcid":false,"given":"Xinxin","family":"Li","sequence":"additional","affiliation":[{"name":"International Center for Aging and Cancer, Hainan Medical University, Haikou 571199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqing","family":"Huang","sequence":"additional","affiliation":[{"name":"Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-Sen University, Guangzhou 510055, China"},{"name":"Department of Temporomandibular Joint, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction & Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, Guangzhou 510180, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songtao","family":"Shi","sequence":"additional","affiliation":[{"name":"Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-Sen University, Guangzhou 510055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruibao","family":"Ren","sequence":"additional","affiliation":[{"name":"International Center for Aging and Cancer, Hainan Medical University, Haikou 571199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e873","DOI":"10.1016\/S2665-9913(25)00105-5","article-title":"The global, regional, and national burden attributable to low bone mineral density, 1990\u20132020: An analysis of a modifiable risk factor from the Global Burden of Disease Study 2021","volume":"7","author":"Hsieh","year":"2025","journal-title":"Lancet Rheumatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"603","DOI":"10.18203\/2319-2003.ijbcp20251847","article-title":"The rising global burden of osteoporosis: Insights into prevalence, fracture rates, and future trends","volume":"14","author":"Vijayakumar","year":"2025","journal-title":"Int. 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