title: Bmp-12 activates tenogenic pathway in human adipose stem cells and affects their immunomodulatory and secretory properties.
abstract: Cell-based therapy is a treatment method in tendon injuries. Bone morphogenic protein 12 (BMP-12) possesses tenogenic activity and was proposed as a differentiating factor for stem cells directed to transplantation. However, BMPs belong to pleiotropic TGF-β superfamily and have diverse effect on cells. Therefore, the aim of this study was to determine if BMP-12 induces tenogenic differentiation of human adipose stem cells (hASCs) and how it affects other features of this population.
  
  
  
  Human ASCs from 6 healthy donors were treated or not with BMP-12 (50 or 100 ng/ml, 7 days) and tested for gene expression (COLL1, SCX, MKH, DCN, TNC, RUNX2), protein expression (COLL1, COLL3, MKH), proliferation, migration, secretory activity, immunomodulatory properties and susceptibility to oxidative stress. RT-PCR revealed up-regulation of SCX, MKH and RUNX2 genes in BMP-12 treated cells (2.05, 2.65 and 1.87 fold in comparison to control, respectively, p < 0.05) and Western Blot revealed significant increase of COLL1 and MHK expression after BMP-12 treatment. Addition of BMP-12 significantly enhanced secretion of VEGF, IL-6, MMP-1 and MPP-8 by hASCs while had no effect on TGF-β, IL-10, EGF and MMP-13. Moreover, BMP-12 presence in medium attenuated inhibitory effect of hASCs on allo-activated lymphocytes proliferation. At the same time BMP-12 displayed no influence on hASCs proliferation, migration and susceptibility to oxidative stress.
  
  
  
  BMP-12 activates tenogenic pathway in hASCs but also affects secretory activity and impairs immunomodulatory potential of this population that can influence the clinical outcome after cell transplantation.
authors.affiliation: Department of Immunology, Transplantology and Internal Medicine, Transplantation Institute, Medical University of Warsaw, Nowogrodzka str. 59, 02-006, Warsaw, Poland.
authors.forename: Weronika
authors.initials: W
authors.lastname: Zarychta-Wiśniewska
authors.affiliation: Department of Immunology, Transplantology and Internal Medicine, Transplantation Institute, Medical University of Warsaw, Nowogrodzka str. 59, 02-006, Warsaw, Poland. anna.burdzinska@wum.edu.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Burdzinska
authors.affiliation: Department of Immunology, Transplantology and Internal Medicine, Transplantation Institute, Medical University of Warsaw, Nowogrodzka str. 59, 02-006, Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Kulesza
authors.affiliation: Department of Immunology, Transplantology and Internal Medicine, Transplantation Institute, Medical University of Warsaw, Nowogrodzka str. 59, 02-006, Warsaw, Poland.
authors.forename: Kamila
authors.initials: K
authors.lastname: Gala
authors.affiliation: Department of Clinical Immunology, Transplantation Institute, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Kaleta
authors.affiliation: Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Warsaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Zielniok
authors.affiliation: Department of Regenerative Medicine, Maria Sklodowska-Curie Memorial Cancer Center, Warsaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Siennicka
authors.affiliation: Department of Immunology, Transplantology and Internal Medicine, Transplantation Institute, Medical University of Warsaw, Nowogrodzka str. 59, 02-006, Warsaw, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Sabat
authors.affiliation: Department of Immunology, Transplantology and Internal Medicine, Transplantation Institute, Medical University of Warsaw, Nowogrodzka str. 59, 02-006, Warsaw, Poland.|Department of Bioinformatics, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Leszek
authors.initials: L
authors.lastname: Paczek
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects*; D015850:Interleukin-6 / Q000378:metabolism; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013710:Tendons / Q000166:cytology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D015850:Interleukin-6; D042461:Vascular Endothelial Growth Factor A; C086559:growth differentiation factor 7; D020784:Matrix Metalloproteinase 8; D020781:Matrix Metalloproteinase 1
keywords: Adipose stem cells; BMP-12; Mesenchymal stem cells; Secretory activity; Tenogenic differentiation