{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T05:05:59Z","timestamp":1781845559049,"version":"3.54.5"},"reference-count":65,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T00:00:00Z","timestamp":1708041600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)\u2014Project","doi-asserted-by":"publisher","award":["429837092"],"award-info":[{"award-number":["429837092"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)\u2014Project","doi-asserted-by":"publisher","award":["202008080032"],"award-info":[{"award-number":["202008080032"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Confocal Microscopy Facility","award":["429837092"],"award-info":[{"award-number":["429837092"]}]},{"name":"Confocal Microscopy Facility","award":["202008080032"],"award-info":[{"award-number":["202008080032"]}]},{"name":"China Scholarship Council (CSC) under Grant","award":["429837092"],"award-info":[{"award-number":["429837092"]}]},{"name":"China Scholarship Council (CSC) under Grant","award":["202008080032"],"award-info":[{"award-number":["202008080032"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Objective: Existing research suggests that bone marrow-derived mesenchymal stem cells (BMSCs) may promote endogenous bone repair. This may be through the secretion of factors that stimulate repair processes or directly through differentiation into osteoblast-progenitor cells. However, the osteogenic potential of BMSCs varies among different tissue sources (e.g., mandibular versus long BMSCs). The main aim of this study was to investigate the difference in osteogenic differentiation capacity between mandibular BMSCs (mBMSCs) and tibial BMSCs (tBMSCs). Materials and Methods: Bioinformatics analysis of the GSE81430 dataset taken from the Gene Expression Omnibus (GEO) database was performed using GEO2R. BMSCs were isolated from mandibular and tibial bone marrow tissue samples. Healthy pigs (n = 3) (registered at the State Office for Nature, Environment, and Consumer Protection, North Rhine-Westphalia (LANUV) 81-02.04.2020.A215) were used for this purpose. Cell morphology and osteogenic differentiation were evaluated in mBMSCs and tBMSCs. The expression levels of toll-like receptor 4 (TLR4) and nuclear transcription factor \u03baB (NF-\u03baB) were analyzed using quantitative polymerase chain reaction (qPCR) and Western blot (WB), respectively. In addition, mBMSC-derived extracellular vesicles (mBMSC-EVs) were gained and used as osteogenic stimuli for tBMSCs. Cell morphology and osteogenic differentiation capacity were assessed after mBMSC-EV stimulation. Results: Bioinformatic analysis indicated that the difference in the activation of the TLR4\/NF-\u03baB pathway was more pronounced compared to all other examined genes. Specifically, this demonstrated significant downregulation, whereas only 5\u20137 upregulated genes displayed significant variances. The mBMSC group showed stronger osteogenic differentiation capacity compared to the tBMSC group, confirmed via ALP, ARS, and von Kossa staining. Furthermore, qPCR and WB analysis revealed a significant decrease in the expression of the TLR4\/NF-\u03baB pathway in the mBMSC group compared to the tBMSC group (TLR4 fold changes: mBMSCs vs. tBMSCs p &lt; 0.05; NF-\u03baB fold changes: mBMSCs vs. tBMSCs p &lt; 0.05). The osteogenic differentiation capacity was enhanced, and qPCR and WB analysis revealed a significant decrease in the expression of TLR4 and NF-\u03baB in the tBMSC group with mBMSC-EVs added compared to tBMSCs alone (TLR4 fold changes: p &lt; 0.05; NF-\u03baB fold changes: p &lt; 0.05). Conclusion: Our results indicate that mBMSC-EVs can promote the osteogenic differentiation of tBMSCs in vitro. The results also provide insights into the osteogenic mechanism of mBMSCs via TLR4\/NF-\u03baB signaling pathway activation. This discovery promises a fresh perspective on the treatment of bone fractures or malunions, potentially offering a novel therapeutic method.<\/jats:p>","DOI":"10.3390\/pharmaceutics16020279","type":"journal-article","created":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T06:00:25Z","timestamp":1708063225000},"page":"279","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Porcine Mandibular Bone Marrow-Derived Mesenchymal Stem Cell (BMSC)-Derived Extracellular Vesicles Can Promote the Osteogenic Differentiation Capacity of Porcine Tibial-Derived BMSCs"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5039-9385","authenticated-orcid":false,"given":"Qun","family":"Zhao","sequence":"first","affiliation":[{"name":"Experimental Orthopedics and Trauma Surgery, University Hospital RWTH Aachen, Pauwelsstra\u00dfe 30, 52074 Aachen, Germany"},{"name":"Department of Orthopedics, Trauma and Reconstructive Surgery, University Hospital RWTH Aachen, Pauwelsstra\u00dfe 30, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Experimental Orthopedics and Trauma Surgery, University Hospital RWTH Aachen, Pauwelsstra\u00dfe 30, 52074 Aachen, Germany"},{"name":"Department of Orthopedics, Trauma and Reconstructive Surgery, University Hospital RWTH Aachen, Pauwelsstra\u00dfe 30, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You","family":"Li","sequence":"additional","affiliation":[{"name":"Experimental Orthopedics and Trauma Surgery, University Hospital RWTH Aachen, Pauwelsstra\u00dfe 30, 52074 Aachen, Germany"},{"name":"Department of Orthopedics, Trauma and Reconstructive Surgery, University Hospital RWTH Aachen, Pauwelsstra\u00dfe 30, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhizhen","family":"He","sequence":"additional","affiliation":[{"name":"Experimental Orthopedics and Trauma Surgery, University Hospital RWTH Aachen, Pauwelsstra\u00dfe 30, 52074 Aachen, Germany"},{"name":"Department of Orthopedics, Trauma and Reconstructive Surgery, University Hospital RWTH Aachen, Pauwelsstra\u00dfe 30, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang","family":"Qin","sequence":"additional","affiliation":[{"name":"Experimental Orthopedics and Trauma Surgery, University Hospital RWTH Aachen, Pauwelsstra\u00dfe 30, 52074 Aachen, Germany"},{"name":"Department of Orthopedics, Trauma and Reconstructive Surgery, University Hospital RWTH Aachen, Pauwelsstra\u00dfe 30, 52074 Aachen, Germany"},{"name":"Department of Shoulder and Elbow Surgery, Center for Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva Miriam","family":"Buhl","sequence":"additional","affiliation":[{"name":"Electron Microscopy Facility, Institute of Pathology and Medical Clinic II, University Hospital RWTH Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00dcmit","family":"Mert","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Trauma and Reconstructive Surgery, University Hospital RWTH Aachen, Pauwelsstra\u00dfe 30, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klemens","family":"Horst","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Trauma and Reconstructive Surgery, University Hospital RWTH Aachen, Pauwelsstra\u00dfe 30, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Hildebrand","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Trauma and Reconstructive Surgery, University Hospital RWTH Aachen, Pauwelsstra\u00dfe 30, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0484-4847","authenticated-orcid":false,"given":"Elizabeth R.","family":"Balmayor","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Trauma and Reconstructive Surgery, University Hospital RWTH Aachen, Pauwelsstra\u00dfe 30, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Greven","sequence":"additional","affiliation":[{"name":"Experimental Orthopedics and Trauma Surgery, University Hospital RWTH Aachen, Pauwelsstra\u00dfe 30, 52074 Aachen, Germany"},{"name":"Department of Orthopedics, Trauma and Reconstructive Surgery, University Hospital RWTH Aachen, Pauwelsstra\u00dfe 30, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ekegren, C., Edwards, E., de Steiger, R., and Gabbe, B. 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