title: Mechanical forces regulate stem cell response to surface topography.
abstract: The interactions between bone tissue and orthopedic implants are strongly affected by mechanical forces at the bone-implant interface, but the interplay between surface topographies, mechanical stimuli, and cell behavior is complex and not well understood yet. This study reports on the influence of mechanical stretch on human mesenchymal stem cells (hMSCs) attached to metallic substrates with different roughness. Controlled forces were applied to plasma membrane of hMSCs cultured on smooth and rough stainless steel surfaces using magnetic collagen-coated particles and an electromagnet system. Degree of phosphorylation of focal adhesion kinase (p-FAK) on the active form (Tyr-397), prostaglandin E2 (PGE2) and vascular endothelial growth factor (VEGF) levels increased on rough samples under static conditions. Cell viability and fibronectin production decreased on rough substrates, while hMSCs maturated to the osteoblastic lineage to a similar extent on both surfaces. PGE2 production and osteoprotegerin/receptor activator of nuclear factor kappa-B ligand ratio increased after force application on both surfaces, although to a greater extent on smooth substrates. p-FAK on Tyr-397 was induced fairly rapidly by mechanical stimulation on rough surfaces while cells cultured on smooth samples failed to activate this kinase in response to tensile forces. Mechanical forces enhanced VEGF secretion and reduced cell viability, fibronetin levels and osteoblastic maturation on smooth surfaces but not on rough samples. The magnetite beads model used in this study is well suited to characterize the response of hMSCs cultured on metallic surfaces to tensile forces and collected data suggest a mechanism whereby mechanotransduction driven by FAK is essential for stem cell growth and functioning on metallic substrates.
authors.affiliation: Unidad de Investigación, Hospital Universitario La Paz-IdiPAZ, Paseo de la Castellana 261, 28046 Madrid, Spain; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Saldaña
authors.forename: Lara
authors.initials: L
authors.lastname: Crespo
authors.forename: Fátima
authors.initials: F
authors.lastname: Bensiamar
authors.forename: Manuel
authors.initials: M
authors.lastname: Arruebo
authors.forename: Nuria
authors.initials: N
authors.lastname: Vilaboa
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation; D013314:Stress, Mechanical; D013499:Surface Properties; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human
keywords: bone; mechanical stretch; mesenchymal stem cells; metals; surface roughness