title: 3, 3', 5-triiodo-L-thyronine Increases In Vitro Chondrogenesis of Mesenchymal Stem Cells From Human Umbilical Cord Stroma Through SRC2.
abstract: Our group focuses on the study of mesenchymal stem cells (MSCs) from human umbilical cord stroma or Warthońs jelly and their directed differentiation toward chondrocyte-like cells capable of regenerating damaged cartilage when transplanted into an injured joint. This study aimed to determine whether lactogenic hormone prolactin (PRL) or 3, 3', 5-triiodo-L-thyronine (T3), the active thyroid hormone, modulates chondrogenesis in our in vitro model of directed chondrogenic differentiation, and whether Wnt signalling is involved in this modulation. MSCs from human umbilical cord stroma underwent directed differentiation toward chondrocyte-like cells by spheroid formation. The addition of T3 to the chondrogenic medium increased the expression of genes linked to chondrogenesis like collagen type 2, integrin alpha 10 beta 1, and Sox9 measured by quantitative real time polymerase chain reaction (qRT-PCR) analysis. Levels of collagen type 2 and aggrecane analyzed by immunohistochemistry, and staining by Safranin O were increased after 14 days in spheroid culture with T3 compared to those without T3 or only with PRL. B-catenin, Frizzled, and GSK-3β gene expressions were significantly higher in spheroids cultured with chondrogenic medium (CM) plus T3 compared to CM alone after 14 days in culture. The increase of chondrogenic differentiation was inhibited when the cells were treated with T3 plus ML151, an inhibitor of the T3 steroid receptor. This work demonstrates, for first time, that T3 promotes differentiation towards chondrocytes-like cells in our in vitro model, that this differentiation is mediated by steroid receptor co-activator 2 (SRC2) and does not induce hypertrophy. J. Cell. Biochem. 117: 2097-2108, 2016. © 2016 Wiley Periodicals, Inc.
authors: Grupo de Terapia Celular y Medicina Regenerativa (TCMR-CHUAC), CIBER-BBN/ISCIII, Servicio de Reumatología, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Departamento de Medicina, Facultade de Oza, Universidade da Coruña (UDC), As Xubias, 15006, A Coruña, Spain.
authors: Pablo
authors: P
authors: Fernández-Pernas
authors: Grupo de Terapia Celular y Medicina Regenerativa (TCMR-CHUAC), CIBER-BBN/ISCIII, Servicio de Reumatología, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Departamento de Medicina, Facultade de Oza, Universidade da Coruña (UDC), As Xubias, 15006, A Coruña, Spain.
authors: Juan
authors: J
authors: Fafián-Labora
authors: Grupo de Terapia Celular y Medicina Regenerativa (TCMR-CHUAC), CIBER-BBN/ISCIII, Servicio de Reumatología, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Departamento de Medicina, Facultade de Oza, Universidade da Coruña (UDC), As Xubias, 15006, A Coruña, Spain.
authors: Iván
authors: I
authors: Lesende-Rodriguez
authors: Grupo de Proteómica-PBR2-ProteoRed/ISCIII-Servicio de Reumatologia, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Universidade da Coruña (UDC), As Xubias, 15006, A Coruña, España.
authors: Jesús
authors: J
authors: Mateos
authors: Grupo de Terapia Celular y Medicina Regenerativa (TCMR-CHUAC), CIBER-BBN/ISCIII, Servicio de Reumatología, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Departamento de Medicina, Facultade de Oza, Universidade da Coruña (UDC), As Xubias, 15006, A Coruña, Spain.
authors: Alexandre
authors: A
authors: De la Fuente
authors: Grupo de Terapia Celular y Medicina Regenerativa (TCMR-CHUAC), CIBER-BBN/ISCIII, Servicio de Reumatología, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Departamento de Medicina, Facultade de Oza, Universidade da Coruña (UDC), As Xubias, 15006, A Coruña, Spain.
authors: Isaac
authors: I
authors: Fuentes
authors: Grupo de Terapia Celular y Medicina Regenerativa (TCMR-CHUAC), CIBER-BBN/ISCIII, Servicio de Reumatología, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Departamento de Medicina, Facultade de Oza, Universidade da Coruña (UDC), As Xubias, 15006, A Coruña, Spain.
authors: Javier
authors: J
authors: De Toro Santos
authors: Grupo de Proteómica-PBR2-ProteoRed/ISCIII-Servicio de Reumatologia, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Universidade da Coruña (UDC), As Xubias, 15006, A Coruña, España.
authors: Fco
authors: F
authors: Blanco García
authors: Grupo de Terapia Celular y Medicina Regenerativa (TCMR-CHUAC), CIBER-BBN/ISCIII, Servicio de Reumatología, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Departamento de Medicina, Facultade de Oza, Universidade da Coruña (UDC), As Xubias, 15006, A Coruña, Spain.
authors: María C
authors: MC
authors: Arufe
mesh_terms: D000943:Antigens, Differentiation / Q000096:biosynthesis; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D020219:Chondrogenesis / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051958:Nuclear Receptor Coactivator 2 / Q000378:metabolism*; D014284:Triiodothyronine / Q000494:pharmacology*; D014470:Umbilical Cord / Q000166:cytology / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000187:drug effects* / Q000502:physiology
chemical_list: D000943:Antigens, Differentiation; C498001:NCOA2 protein, human; D051958:Nuclear Receptor Coactivator 2; D014284:Triiodothyronine
keywords: 3, 3′, 5-TRIIODO-L-THYRONINE; CHONDROCYTE-LIKE CELLS; CHONDROGENESIS; HUMAN UMBILICAL CORD STROMA; MESENCHYMAL STEM CELLS; PROLACTIN