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人间充质干细胞对周期性拉伸应变的反应中促炎细胞因子的表达。

Expression of proinflammatory cytokines by human mesenchymal stem cells in response to cyclic tensile strain.

作者信息

Sumanasinghe Ruwan D, Pfeiler T Wayne, Monteiro-Riviere Nancy A, Loboa Elizabeth G

机构信息

Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, North Carolina 27695-7115, USA.

出版信息

J Cell Physiol. 2009 Apr;219(1):77-83. doi: 10.1002/jcp.21653.

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.

摘要

间充质干细胞在正常生长过程中会产生促炎细胞因子。已有报道称这些细胞因子可直接或间接调节骨吸收。然而,体外骨组织工程中使用的成骨条件(化学和/或机械条件)对人骨髓间充质干细胞(hMSCs)细胞因子表达的影响尚未得到研究。在本研究中,我们调查了循环拉伸应变、培养基(含和不含地塞米松)以及培养持续时间对骨髓来源的人骨髓间充质干细胞(hMSCs)肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和白细胞介素-8(IL-8)表达的影响。接种在三维I型胶原基质中的人骨髓间充质干细胞在完全生长培养基或含地塞米松的成骨培养基中,于1 Hz下分别承受0%、10%和12%的单轴循环拉伸应变,每天4小时,持续7天和14天。无论应变水平和培养基条件如何,hMSCs的活力均得以维持。在本研究调查的任何条件下,hMSCs中均未观察到TNF-α或IL-1β的表达。IL-6的表达取决于培养基。10%和12%的应变水平均导致IL-6表达增加。10%和12%的应变水平均导致hMSCs产生的IL-8增加,且这种增加依赖于地塞米松的存在。hMSCs的IL-6和IL-8表达由循环拉伸应变和成骨分化培养基诱导,表明IL-6和IL-8可能在hMSCs成骨分化过程中作为自分泌信号发挥作用。

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