PMID- 30654712 OWN - NLM STAT- MEDLINE DCOM- 20200312 LR - 20200312 IS - 1557-8534 (Electronic) IS - 1547-3287 (Linking) VI - 28 IP - 6 DP - 2019 Mar 15 TI - Activin Receptor 2 Antagonization Impairs Adipogenic and Enhances Osteogenic Differentiation in Mouse Adipose-Derived Stem Cells and Mouse Bone Marrow-Derived Stem Cells In Vitro and In Vivo. PG - 384-397 LID - 10.1089/scd.2018.0155 [doi] AB - Tumors, traumata, burn injuries or surgeries can lead to critical-sized bony defects which need to be reconstructed. Mesenchymal stem cells (MSCs) have the ability to differentiate into multiple cell lineages and thus present a promising alternative for use in tissue engineering and reconstruction. However, there is an ongoing debate whether all MSCs are equivalent in their differentiation and proliferation ability. The goal of this study was to assess osteogenic and adipogenic characteristic changes of adipose-derived stem cells (ASCs) and bone marrow-derived stem cells (BMSCs) upon Myostatin inhibition with Follistatin in vitro and in vivo. We harvested ASCs from mice inguinal fat pads and BMSCs from tibiae of mice. By means of histology, real-time cell analysis, immunohistochemistry, and PCR osteogenic and adipogenic proliferation and differentiation in the presence or absence of Follistatin were analyzed. In vivo, osteogenic capacity was investigated in a tibial defect model of wild-type (WT) mice treated with mASCs and mBMSCs of Myo(-/-) and WT origin. In vitro, we were able to show that inhibition of Myostatin leads to markedly reduced proliferative capacity in mBMSCs and mASCs in adipogenic differentiation and reduced proliferation in osteogenic differentiation in mASCs, whereas proliferation in mBMSCs in osteogenic differentiation was increased. Adipogenic differentiation was inhibited in mASCs and mBMSCs upon Follistatin treatment, whereas osteogenic differentiation was increased in both cell lineages. In vivo, we could demonstrate increased osteoid formation in WT mice treated with mASCs and mBMSCs of Myo(-/-) origin and enhanced osteogenic differentiation and proliferation of mASCs of Myo(-/-) origin. We could demonstrate that the osteogenic potential of mASCs could be raised to a level comparable to mBMSCs upon inhibition of Myostatin. Moreover, Follistatin treatment led to inhibition of adipogenesis in both lineages. FAU - Wallner, Christoph AU - Wallner C AD - Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany. FAU - Huber, Julika AU - Huber J AD - Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany. FAU - Drysch, Marius AU - Drysch M AD - Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany. FAU - Schmidt, Sonja Verena AU - Schmidt SV AD - Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany. FAU - Wagner, Johannes Maximilian AU - Wagner JM AD - Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany. FAU - Dadras, Mehran AU - Dadras M AD - Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany. FAU - Dittfeld, Stephanie AU - Dittfeld S AD - Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany. FAU - Becerikli, Mustafa AU - Becerikli M AD - Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany. FAU - Jaurich, Henriette AU - Jaurich H AD - Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany. FAU - Lehnhardt, Marcus AU - Lehnhardt M AD - Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany. FAU - Behr, Bjorn AU - Behr B AD - Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190220 PL - United States TA - Stem Cells Dev JT - Stem cells and development JID - 101197107 RN - 0 (Follistatin) RN - EC 2.7.11.30 (Activin Receptors) SB - IM MH - Activin Receptors/*antagonists & inhibitors/genetics/metabolism MH - Adipogenesis/*drug effects/genetics MH - Adipose Tissue/cytology/*metabolism MH - Animals MH - Bone Marrow Cells/cytology/*metabolism MH - Cell Differentiation/*drug effects/genetics MH - Female MH - Follistatin/*pharmacology MH - Mice MH - Mice, Knockout MH - Osteogenesis/*drug effects/genetics MH - Stem Cells/cytology/*metabolism OTO - NOTNLM OT - MSC OT - adipogenesis OT - differentiation OT - osteogenesis EDAT- 2019/01/19 06:00 MHDA- 2020/03/13 06:00 CRDT- 2019/01/19 06:00 PHST- 2019/01/19 06:00 [pubmed] PHST- 2020/03/13 06:00 [medline] PHST- 2019/01/19 06:00 [entrez] AID - 10.1089/scd.2018.0155 [doi] PST - ppublish SO - Stem Cells Dev. 2019 Mar 15;28(6):384-397. doi: 10.1089/scd.2018.0155. Epub 2019 Feb 20.