Continuous Low-Intensity Ultrasound Preserves Chondrogenesis of Mesenchymal Stromal Cells in the Presence of Cytokines by Inhibiting NFκB Activation.
Continuous Low-Intensity Ultrasound Preserves Chondrogenesis of Mesenchymal Stromal Cells in the Presence of Cytokines by Inhibiting NFκB Activation.
复制标题
DOI：
10.3390/biom12030434
复制
发表时间：
2022-03-11
期刊：
影响因子：
5.5
通讯作者：
Subramanian A
中科院分区：
文献类型：
--
作者：
Bhogoju S;Khan S;Subramanian A
促炎关节环境，加上间充质干细胞（MSCs）软骨分化受阻，导致软骨修复效果不佳。磷酸化 - NFκB的核转位下调SOX9并阻碍MSCs的软骨形成。减少NFκB有害影响同时促进MSCs软骨形成的策略备受关注。本研究证实了连续低强度超声（cLIUS）在促炎环境中维持MSCs软骨形成的能力。将MSCs接种在藻酸盐：胶原蛋白水凝胶中，并在存在白细胞介素1β（IL1β）的情况下于超声辅助生物反应器（5.0 MHz，2.5 Vpp；每天4次）中培养21天，通过实时定量聚合酶链反应（qRT - PCR）和免疫荧光进行评估。在单次暴露于cLIUS后评估与NFκB通路相关标志物的差异表达，并通过蛋白质印迹法、qRT - PCR和免疫荧光进行检测。通过四甲基罗丹明甲酯（TMRM）测定法评估线粒体电位。cLIUS的软骨诱导潜力通过SOX9和Ⅱ型胶原蛋白（COLII）表达增加得以体现。cLIUS通过启动IκBα反馈机制稳定细胞质中的NFκB复合物，从而防止其核转位，扩展了其软骨保护作用。cLIUS通过在促炎环境中恢复线粒体电位和线粒体mRNA表达，起到线粒体保护剂的作用。总之，我们的结果证明了cLIUS在促炎条件下用于软骨修复和再生的潜力。
Proinflammatory joint environment, coupled with impeded chondrogenic differentiation of mesenchymal stromal cells (MSCs), led to inferior cartilage repair outcomes. Nuclear translocation of phosphorylated-NFκB downregulates SOX9 and hinders the chondrogenesis of MSCs. Strategies that minimize the deleterious effects of NFκB, while promoting MSC chondrogenesis, are of interest. This study establishes the ability of continuous low-intensity ultrasound (cLIUS) to preserve MSC chondrogenesis in a proinflammatory environment. MSCs were seeded in alginate:collagen hydrogels and cultured for 21 days in an ultrasound-assisted bioreactor (5.0 MHz, 2.5 Vpp; 4 applications/day) in the presence of IL1β and evaluated by qRT-PCR and immunofluorescence. The differential expression of markers associated with the NFκB pathway was assessed upon a single exposure of cLIUS and assayed by Western blotting, qRT-PCR, and immunofluorescence. Mitochondrial potential was evaluated by tetramethylrhodamine methyl ester (TMRM) assay. The chondroinductive potential of cLIUS was noted by the increased expression of SOX9 and COLII. cLIUS extended its chondroprotective effects by stabilizing the NFκB complex in the cytoplasm via engaging the IκBα feedback mechanism, thus preventing its nuclear translocation. cLIUS acted as a mitochondrial protective agent by restoring the mitochondrial potential and the mitochondrial mRNA expression in a proinflammatory environment. Altogether, our results demonstrated the potential of cLIUS for cartilage repair and regeneration under proinflammatory conditions.
登录
查看更多内容
影响因子：
5.6
作者：
Kanichai, Manoj;Ferguson, Damien;Campbell, Veronica A.
通讯作者：
Campbell, Veronica A.
影响因子：
2.4
作者：
Lee, Hyun Jung;Choi, Byung Hyune;Park, So Ra
通讯作者：
Park, So Ra
影响因子：
4.8
作者：
Murakami, S;Lefebvre, V;de Crombrugghe, B
通讯作者：
de Crombrugghe, B
影响因子：
10.5
作者：
Sitcheran, R;Cogswell, PC;Baldwin, AS
通讯作者：
Baldwin, AS
影响因子：
--
作者：
Cui, JH;Park, K;Min, BH
通讯作者：
Min, BH