title: Differential Expression of Adhesion-Related Proteins and MAPK Pathways Lead to Suitable Osteoblast Differentiation of Human Mesenchymal Stem Cells Subpopulations.
abstract: Cellular adhesion enables communication between cells and their environment. Adhesion can be achieved throughout focal adhesions and its components influence osteoblast differentiation of human mesenchymal stem cells (hMSCs). Because cell adhesion and osteoblast differentiation are closely related, this article aimed to analyze the expression profiles of adhesion-related proteins during osteoblastic differentiation of two hMSCs subpopulations (CD105(+) and CD105(-)) and propose a strategy for assembling bone grafts based on its adhesion ability. In vitro experiments of osteogenic differentiation in CD105(-) cells showed superior adhesion efficiency and 2-fold increase of α-actinin expression compared with CD105(+) cells at the maturation stage. Interestingly, levels of activated β1-integrin increased in CD105(-) cells during the process. Additionally, the CD105(-) subpopulation showed 3-fold increase of phosphorylated FAK(Y397) compared to CD105(+) cells. Results also indicate that ERK1/2 was activated during CD105(-) bone differentiation and participation of mitogen-activated protein kinase (MAPK)-p38 in CD105(+) differentiation through a focal adhesion kinase (FAK)-independent pathway. In vivo trial demonstrated that grafts containing CD105(-) showed osteocytes embedded in a mineralized matrix, promoted adequate graft integration, increased host vascular infiltration, and efficient intramembranous repairing. In contrast, grafts containing CD105(+) showed deficient endochondral ossification and fibrocartilaginous tissue. Based on the expression of α-actinin, FAKy,(397) and ERK1/2 activation, we define maturation stage as critical for bone graft assembling. By in vitro assays, CD105(-) subpopulation showed superior adhesion efficiency compared to CD105(+) cells. Considering in vitro and in vivo assays, this study suggests that integration of a scaffold with CD105(-) subpopulation at the maturation stage represents an attractive strategy for clinical use in orthopedic bioengineering.
authors.affiliation: 1 Laboratorio de Biología Molecular e Histocompatibilidad, Dirección de Investigación Hospital General "Dr. Manuel Gea González ," México City, México .
authors.forename: Margarita
authors.initials: M
authors.lastname: Leyva-Leyva
authors.affiliation: 1 Laboratorio de Biología Molecular e Histocompatibilidad, Dirección de Investigación Hospital General "Dr. Manuel Gea González ," México City, México .
authors.forename: Annia
authors.initials: A
authors.lastname: López-Díaz
authors.affiliation: 2 Laboratorio de Inmunología Integrativa, Instituto Nacional de Enfermedades Respiratorias "Ismael Cosío Villegas ," México City, México .
authors.forename: Lourdes
authors.initials: L
authors.lastname: Barrera
authors.affiliation: 3 Departamento de Bioquímica y Medicina Molecular, Universidad Autónoma de Nuevo León (UANL) , Monterrey, México .|4 Unidad de Neurociencias, Centro de Investigación y Desarrollo en Ciencias de la Salud, Universidad Autónoma de Nuevo León (UANL) , Monterrey, México .
authors.forename: Alberto
authors.initials: A
authors.lastname: Camacho-Morales
authors.affiliation: 1 Laboratorio de Biología Molecular e Histocompatibilidad, Dirección de Investigación Hospital General "Dr. Manuel Gea González ," México City, México .
authors.forename: Felipe
authors.initials: F
authors.lastname: Hernandez-Aguilar
authors.affiliation: 1 Laboratorio de Biología Molecular e Histocompatibilidad, Dirección de Investigación Hospital General "Dr. Manuel Gea González ," México City, México .
authors.forename: Erika M
authors.initials: EM
authors.lastname: Carrillo-Casas
authors.affiliation: 5 Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades Centro Médico Nacional Siglo XXI , IMSS, México City, México .
authors.forename: Lourdes
authors.initials: L
authors.lastname: Arriaga-Pizano
authors.affiliation: 6 División de Ginecología y Obstetricia, Hospital General "Dr. Manuel Gea González ," México City, México .
authors.forename: Jaime
authors.initials: J
authors.lastname: Calderón-Pérez
authors.affiliation: 7 Laboratorio de Bioquímica, Facultad de Ciencias, Universidad Nacional Autónoma de México (UNAM) , México City, México .
authors.forename: Jorge
authors.initials: J
authors.lastname: García-Álvarez
authors.affiliation: 8 Instituto de Fisiología Celular, Universidad Nacional Autónoma de México (UNAM) , México City, México .
authors.forename: Gabriel
authors.initials: G
authors.lastname: Orozco-Hoyuela
authors.affiliation: 9 Instituto de Investigaciones en Materiales, Universidad Nacional Autónoma de México (UNAM) , México City, México .
authors.forename: Cristina
authors.initials: C
authors.lastname: Piña-Barba
authors.affiliation: 3 Departamento de Bioquímica y Medicina Molecular, Universidad Autónoma de Nuevo León (UANL) , Monterrey, México .|10 Unidad de Terapias Experimentales, Centro de Investigación y Desarrollo en Ciencias de la Salud, Universidad Autónoma de Nuevo León (UANL) , Monterrey, México .
authors.forename: Augusto
authors.initials: A
authors.lastname: Rojas-Martínez
authors.affiliation: 11 Departamento de Histología, Facultad de Medicina , UANL, Monterrey, México .|12 Unidad de Bioimágen, Centro de Investigación y Desarrollo en Ciencias de la Salud, Universidad Autónoma de Nuevo León (UANL) , Monterrey, México .
authors.forename: Víktor
authors.initials: V
authors.lastname: Romero-Díaz
authors.affiliation: 13 Laboratorio de Ingeniería Tisular-Banco de Hueso y Tejidos, Servicio de Ortopedia y Traumatología, Hospital Universitario "Dr. José E. González ," Monterrey, México .
authors.forename: Jorge
authors.initials: J
authors.lastname: Lara-Arias
authors.affiliation: 3 Departamento de Bioquímica y Medicina Molecular, Universidad Autónoma de Nuevo León (UANL) , Monterrey, México .|10 Unidad de Terapias Experimentales, Centro de Investigación y Desarrollo en Ciencias de la Salud, Universidad Autónoma de Nuevo León (UANL) , Monterrey, México .
authors.forename: Nancy
authors.initials: N
authors.lastname: Rivera-Bolaños
authors.affiliation: 14 Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México , México City, México .
authors.forename: César
authors.initials: C
authors.lastname: López-Camarillo
authors.affiliation: 3 Departamento de Bioquímica y Medicina Molecular, Universidad Autónoma de Nuevo León (UANL) , Monterrey, México .|10 Unidad de Terapias Experimentales, Centro de Investigación y Desarrollo en Ciencias de la Salud, Universidad Autónoma de Nuevo León (UANL) , Monterrey, México .
authors.forename: Nidia
authors.initials: N
authors.lastname: Moncada-Saucedo
authors.affiliation: 3 Departamento de Bioquímica y Medicina Molecular, Universidad Autónoma de Nuevo León (UANL) , Monterrey, México .|10 Unidad de Terapias Experimentales, Centro de Investigación y Desarrollo en Ciencias de la Salud, Universidad Autónoma de Nuevo León (UANL) , Monterrey, México .
authors.forename: Alejandra
authors.initials: A
authors.lastname: Galván-De los Santos
authors.affiliation: 1 Laboratorio de Biología Molecular e Histocompatibilidad, Dirección de Investigación Hospital General "Dr. Manuel Gea González ," México City, México .
authors.forename: Fátima
authors.initials: F
authors.lastname: Meza-Urzúa
authors.affiliation: 15 Centro de Ingeniería y Tecnología (CITEC), Universidad Autónoma de Baja California , Baja California, Tijuana, México .
authors.forename: Luis
authors.initials: L
authors.lastname: Villarreal-Gómez
authors.affiliation: 3 Departamento de Bioquímica y Medicina Molecular, Universidad Autónoma de Nuevo León (UANL) , Monterrey, México .|10 Unidad de Terapias Experimentales, Centro de Investigación y Desarrollo en Ciencias de la Salud, Universidad Autónoma de Nuevo León (UANL) , Monterrey, México .
authors.forename: Lizeth
authors.initials: L
authors.lastname: Fuentes-Mera
mesh_terms: D002448:Cell Adhesion / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010006:Osteoblasts / Q000166:cytology*; D010012:Osteogenesis / Q000502:physiology*; D010766:Phosphorylation; D015398:Signal Transduction / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D051416:Focal Adhesion Protein-Tyrosine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases