title: Expression of proinflammatory cytokines by human mesenchymal stem cells in response to cyclic tensile strain.
abstract: Mesenchymal stem cells produce proinflammatory cytokines during their normal growth. Direct or indirect regulation of bone resorption by these cytokines has been reported. However, the effects of osteogenic conditions-chemical and/or mechanical-utilized during in vitro bone tissue engineering on expression of cytokines by hMSCs have not been studied. In this study, we investigated the effects of cyclic tensile strain, culture medium (with and without dexamethasone), and culture duration on the expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and interleukin-8 (IL-8) by bone marrow derived human mesenchymal stem cells (hMSCs). Human MSCs seeded in three-dimensional Type I collagen matrices were subjected to 0%, 10%, and 12% uniaxial cyclic tensile strains at 1 Hz for 4 h/day for 7 and 14 days in complete growth or dexamethasone-containing osteogenic medium. Viability of hMSCs was maintained irrespective of strain level and media conditions. Expression of either TNF-alpha or IL-1 beta was not observed in hMSCs under any of the conditions investigated in this study. Expression of IL-6 was dependent on culture medium. An increase in IL-6 expression was caused by both 10% and 12% strain levels. Both 10% and 12% strain levels caused an increase in IL-8 production by hMSCs that was dependent on the presence of dexamethasone. IL-6 and IL-8 expressions by hMSCs were induced by cyclic tensile strain and osteogenic differentiating media, indicating that IL-6 and IL-8 may be functioning as autocrine signals during osteogenic differentiation of hMSCs.
authors.affiliation: Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, North Carolina 27695-7115, USA.
authors.forename: Ruwan D
authors.initials: RD
authors.lastname: Sumanasinghe
authors.forename: T Wayne
authors.initials: TW
authors.lastname: Pfeiler
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Monteiro-Riviere
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Loboa
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D013314:Stress, Mechanical; D013312:Stress, Physiological; D013718:Tensile Strength; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D055815:Young Adult
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha