{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T01:23:08Z","timestamp":1783128188834,"version":"3.54.6"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T00:00:00Z","timestamp":1680652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioeng. Biotechnol."],"abstract":"<jats:p><jats:bold>Introduction:<\/jats:bold>This study aimed to determine whether miR-20 promoted osteogenic differentiation in bone marrow-derived mesenchymal stem\/stromal cells (BMSCs) and accelerated bone formation in the maxillary sinus bone defect model in rabbits.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold>BMSCs were transfected with miR-20a or anti-miR-20a for 12\u00a0h, followed by detection of RUNX2, Sp7 mRNA, bone morphogenetic protein 2 (BMP2), and RUNX2 protein expression. Alkaline phosphatase (ALP) activity and Alizarin Red S staining were used to detect calcified nodule deposition. In the rabbit maxillary sinus bone defect model, miR-20a loaded with AAV and BMP2 protein were mixed with Bio-Oss bone powder for filling the bone defect. At 4\u00a0weeks and 8\u00a0weeks, bone density was detected by cone beam computed tomography (CBCT), and new bone, osteoblasts, and collagen type 1 were evaluated by hematoxylin and eosin (HE) staining and immunohistochemical (IHC) staining.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold>Overexpression of miR-20a enhanced the mRNA and protein levels of BMP2, RUNX2, and SP7, the activity of ALP, and the levels of matrix mineralization, whereas the levels and activity of the aforementioned factors were decreased by anti-miR-20a treatment of BMSCs. Furthermore, miR-20a significantly increased the bone density, the number of osteoblasts, and the secretion of collagen type 1 in bone defects compared with Bio-Oss bone powder in the rabbit maxillary sinus bone defect model.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold>Overall, miR-20a can induce osteogenic differentiation in BMSCs and accelerate bone formation of maxillary sinus defects in rabbits.<\/jats:p>","DOI":"10.3389\/fbioe.2023.1127908","type":"journal-article","created":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T04:52:17Z","timestamp":1680670337000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["MiR-20a promotes osteogenic differentiation in bone marrow-derived mesenchymal stem\/stromal cells and bone repair of the maxillary sinus defect model in rabbits"],"prefix":"10.3389","volume":"11","author":[{"given":"Yi-Xuan","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhu-Li","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Wen","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Jun","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Ai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Hui","family":"Mai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,4,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"468","DOI":"10.4103\/jisp.jisp_236_18","article-title":"Maxillary sinus augmentation","volume":"22","author":"Bathla","year":"2018","journal-title":"J. Indian Soc. Periodontol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s40902-016-0064-2","article-title":"Frequency of bone graft in implant surgery","volume":"38","author":"Cha","year":"2016","journal-title":"Maxillofac. Plast. Reconstr. Surg."},{"key":"B3","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1016\/j.ymthe.2017.11.018","article-title":"Global MicroRNA profiling in human bone marrow skeletal-stromal or mesenchymal-stem cells identified candidates for bone regeneration","volume":"26","author":"Chang","year":"2018","journal-title":"Mol. Ther."},{"key":"B4","doi-asserted-by":"publisher","first-page":"81","DOI":"10.3892\/etm.2020.9208","article-title":"Osteogenic differentiation and inflammatory response of recombinant human bone morphogenetic protein-2 in human maxillary sinus membrane-derived cells","volume":"20","author":"Chun","year":"2020","journal-title":"Exp. Ther. Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1016\/j.bjoms.2016.05.008","article-title":"A comprehensive clinical review of maxillary sinus floor elevation: Anatomy, techniques, biomaterials and complications","volume":"54","author":"Danesh-Sani","year":"2016","journal-title":"Br. J. Oral Maxillofac. Surg."},{"key":"B6","doi-asserted-by":"publisher","first-page":"3303","DOI":"10.26355\/eurrev_201806_15149","article-title":"MiR-374b promotes osteogenic differentiation of MSCs by degrading PTEN and promoting fracture healing","volume":"22","author":"Ge","year":"2018","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"5935","DOI":"10.1038\/s41598-020-62407-y","article-title":"Therapeutic outcomes of non-grafted and platelet concentrations-grafted transcrestal maxillary sinus elevation (tsfe): A systematic review and meta-analysis","volume":"10","author":"Guo","year":"2020","journal-title":"Sci. Rep."},{"key":"B8","first-page":"61","article-title":"The negative effect of combining rhBMP-2 and Bio-Oss on bone formation for maxillary sinus augmentation","volume":"32","author":"Kao","year":"2012","journal-title":"Int. J. Periodontics Restor. Dent."},{"key":"B9","doi-asserted-by":"publisher","first-page":"158S","DOI":"10.1177\/0022034515594573","article-title":"Efficacy of rhBMP-2\/hydroxyapatite on sinus floor augmentation: A multicenter, randomized controlled clinical trial","volume":"94","author":"Kim","year":"","journal-title":"J. Dent. Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1361","DOI":"10.1111\/clr.12471","article-title":"Prospective randomized, controlled trial of sinus grafting using Escherichia-coli-produced rhBMP-2 with a biphasic calcium phosphate carrier compared to deproteinized bovine bone","volume":"26","author":"Kim","year":"","journal-title":"Clin. Oral Implants Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"921","DOI":"10.23812\/20-604-A","article-title":"MicroRNA-20a suppresses RANKL-modulated osteoclastogenesis and prevents bone erosion in mice with rheumatoid arthritis through the TLR4\/p38 pathway","volume":"35","author":"Kong","year":"2021","journal-title":"J. Biol. Regul. Homeost. Agents"},{"key":"B12","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1111\/j.1600-0501.2011.02419.x","article-title":"Sinus augmentation using rhbmp-2\/ACS in a mini-pig model: Relative efficacy of autogenous fresh particulate iliac bone grafts","volume":"24","author":"Lee","year":"2013","journal-title":"Clin. Oral Implants Res."},{"key":"B13","doi-asserted-by":"publisher","first-page":"e12697","DOI":"10.1111\/cpr.12697","article-title":"MicroRNA-21 affects mechanical force-induced midpalatal suture remodelling","volume":"53","author":"Li","year":"2020","journal-title":"Cell Prolif."},{"key":"B14","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1159\/000506304","article-title":"Effect of MicroRNA-20a on osteogenic differentiation of human adipose tissue-derived stem cells","volume":"208","author":"Luo","year":"2020","journal-title":"Cells Tissues Organs"},{"key":"B15","doi-asserted-by":"publisher","first-page":"683","DOI":"10.21037\/atm-22-2753","article-title":"MiR-20a: A mechanosensitive microRNA that regulates fluid shear stress-mediated osteogenic differentiation via the BMP2 signaling pathway by targeting BAMBI and SMAD6","volume":"10","author":"Mai","year":"2022","journal-title":"Ann. Transl. Med."},{"key":"B16","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.3760\/cma.j.issn.0366-6999.20123137","article-title":"miRNA expression profile during fluid shear stress-induced osteogenic differentiation in MC3T3-E1 cells file during fluid shear stress-induced osteogenic differentiation in MC3T3-E1 cells","volume":"126","author":"Mai","year":"2013","journal-title":"Chin. Med. J. (Engl.)"},{"key":"B17","doi-asserted-by":"publisher","first-page":"7589072","DOI":"10.1155\/2020\/7589072","article-title":"The effect of autologous platelet concentrates on maxillary sinus augmentation: A meta-analysis of randomized controlled trials and systematic review","volume":"2020","author":"Meng","year":"2020","journal-title":"Biomed. Res. Int."},{"key":"B18","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1007\/s00223-018-0410-8","article-title":"MicroRNA-218 promotes osteogenic differentiation of mesenchymal stem cells and accelerates bone fracture healing","volume":"103","author":"Shi","year":"2018","journal-title":"Calcif. Tissue Int."},{"key":"B19","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1007\/s11010-019-03578-9","article-title":"MiR-26a promotes fracture healing of nonunion rats possibly by targeting SOSTDC1 and further activating Wnt\/\u03b2-catenin signaling pathway","volume":"460","author":"Sun","year":"2019","journal-title":"Mol. Cell Biochem."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2015\/412327","article-title":"mir-21 overexpressing mesenchymal stem cells accelerate fracture healing in a rat closed femur fracture model","volume":"2015","author":"Sun","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1111\/jcpe.12921","article-title":"Sinus augmentation using rhBMP-2\/ACS in a mini-pig model: Influence of an adjunctive ceramic bone biomaterial","volume":"45","author":"Susin","year":"2018","journal-title":"J. Clin. Periodontol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1097\/ID.0b013e31829262a8","article-title":"Effect of rhbmp-2 upon maxillary sinus augmentation: A comprehensive review[J]","volume":"22","author":"Torrecillas-Martinez","year":"2013","journal-title":"Implant Dent."},{"key":"B23","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1038\/s41419-017-0210-5","article-title":"Osteoblast-targeted delivery of miR-33-5p attenuates osteopenia development induced by mechanical unloading in mice","volume":"9","author":"Wang","year":"2018","journal-title":"Cell Death Dis."},{"key":"B24","doi-asserted-by":"publisher","first-page":"4271","DOI":"10.3892\/mmr.2019.10676","article-title":"MicroRNA-20a negatively regulates the growth and osteoclastogenesis of THP-1 cells by downregulating PPAR\u03b3","volume":"20","author":"Wang","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"B25","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1186\/s13287-021-02501-8","article-title":"miR-20a-5p contributes to osteogenic differentiation of human dental pulp stem cells by regulating BAMBI and activating the phosphorylation of Smad5 and p38","volume":"12","author":"Xiao","year":"2021","journal-title":"Stem Cell Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1186\/s13287-019-1168-2","article-title":"miRNA-21 promotes osteogenesis via the PTEN\/PI3K\/Akt\/HIF-1\u03b1 pathway and enhances bone regeneration in critical size defects","volume":"10","author":"Yang","year":"2019","journal-title":"Stem Cell Res. Ther."},{"key":"B27","doi-asserted-by":"publisher","first-page":"857","DOI":"10.3892\/ijmm.2019.4249","article-title":"The role of antimiR-26a-5p\/biphasic calcium phosphate in repairing rat femoral defects","volume":"44","author":"Yuan","year":"2019","journal-title":"Int. J. Mol. Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"829","DOI":"10.4161\/rna.8.5.16043","article-title":"MiRNA-20a promotes osteogenic differentiation of human mesenchymal stem cells by co-regulating BMP signaling","volume":"8","author":"Zhang","year":"2011","journal-title":"RNA Biol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"10376","DOI":"10.1038\/ncomms10376","article-title":"Cell-free 3D scaffold with two-stage delivery of miRNA-26a to regenerate critical-sized bone defects","volume":"7","author":"Zhang","year":"2016","journal-title":"Nat. Commun."},{"key":"B30","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1007\/s12020-013-9986-y","article-title":"MicroRNA-17-92 cluster regulates osteoblast proliferation and differentiation","volume":"45","author":"Zhou","year":"2014","journal-title":"Endocrine"}],"container-title":["Frontiers in Bioengineering and Biotechnology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbioe.2023.1127908\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T18:40:29Z","timestamp":1729190429000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbioe.2023.1127908\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,5]]},"references-count":30,"alternative-id":["10.3389\/fbioe.2023.1127908"],"URL":"https:\/\/doi.org\/10.3389\/fbioe.2023.1127908","relation":{},"ISSN":["2296-4185"],"issn-type":[{"value":"2296-4185","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,5]]},"article-number":"1127908"}}