Moderate dynamic compression inhibits pro-catabolic response of cartilage to mechanical injury, tumor necrosis factor-α and interleukin-6, but accentuates degradation above a strain threshold.

Moderate dynamic compression inhibits pro-catabolic response of cartilage to mechanical injury, tumor necrosis factor-α and interleukin-6, but accentuates degradation above a strain threshold.
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中等动态压缩抑制软骨对机械损伤,肿瘤坏死因子-α和白介素-6的促代谢反应,但突出了应变阈值以上的降解。

DOI:
10.1016/j.joca.2013.08.021
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发表时间:
2013-12
影响因子:
7
通讯作者:
Grodzinsky, A. J.
Grodzinsky, A. J.
中科院分区:
医学2区
文献类型:
--
作者:
Li, Y.;Frank, E. H.;Wang, Y.;Chubinskaya, S.;Huang, H. -H.;Grodzinsky, A. J.

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创伤性关节损伤可在炎性细胞因子升高的情况下引发早期软骨退化(例如,TNF-α和IL-6)。损伤后动态载荷对体内软骨降解和修复的积极/消极影响尚未得到很好的理解。本研究观察了动态应变对体外培养的未成熟牛软骨的影响,并与TNF-α + IL-6及其可溶性受体(sIL-6 R)联合作用。将机械损伤或未损伤的外植体组在TNF-α + IL-6/sIL-6 R中培养8天。在10%、20%或30%应变幅度下同时施加间歇动态压缩。结果测量包括sGAG损失(DMMB)、聚集蛋白聚糖生物合成(35 S-掺入)、聚集蛋白聚糖酶活性(Western印迹)、软骨细胞活力(荧光染色)和凋亡(通过光学显微镜观察的核起泡)以及基因表达(qPCR)。在牛外植体中,单独的精氨酸和损伤加细胞因子处理显著增加sGAG损失和聚集蛋白聚糖酶活性,并诱导软骨细胞凋亡。10%和20%的中度菌株可消除这些效应。然而,30%的应变振幅大大增加细胞凋亡,并没有对聚集蛋白聚糖酶活性的抑制作用。TNF+IL-6/sIL-6 R下调基质基因表达,上调炎症基因表达,中度动力菌株可挽救这种效应,但30%菌株不能。适度的动态压缩抑制软骨对机械损伤和细胞因子挑战的促分解代谢反应,但是存在阈值应变振幅,高于该阈值应变振幅,负荷变得对软骨有害。我们的研究结果支持的概念,适当的负荷伤后康复。
Traumatic joint injury can initiate early cartilage degeneration in the presence of elevated inflammatory cytokines (e.g., TNF-α and IL-6). The positive/negative effects of post-injury dynamic loading on cartilage degradation and repair in vivo is not well-understood. This study examined the effects of dynamic strain on immature bovine cartilage in vitro challenged with TNF-α + IL-6 and its soluble receptor (sIL-6R) with/without initial mechanical injury. Groups of mechanically injured or non-injured explants were cultured in TNF-α + IL-6/sIL-6R for 8 days. Intermittent dynamic compression was applied concurrently at 10%, 20%, or 30% strain amplitude. Outcome measures included sGAG loss (DMMB), aggrecan biosynthesis (35S-incorporation), aggrecanase activity (Western blot), chondrocyte viability (fluorescence staining) and apoptosis (nuclear blebbing via light microscopy), and gene expression (qPCR). In bovine explants, cytokine-alone and injury-plus-cytokine treatments markedly increased sGAG loss and aggrecanase activity, and induced chondrocyte apoptosis. These effects were abolished by moderate 10% and 20% strains. However, 30% strain-amplitude greatly increased apoptosis and had no inhibitory effect on aggrecanase activity. TNF+IL-6/sIL-6R downregulated matrix gene expression and upregulated expression of inflammatory genes, effects that were rescued by moderate dynamic strains but not by 30% strain. Moderate dynamic compression inhibits the pro-catabolic response of cartilage to mechanical injury and cytokine challenge, but there is a threshold strain-amplitude above which loading becomes detrimental to cartilage. Our findings support the concept of appropriate loading for post-injury rehabilitation.
DOI: 10.1074/jbc.m400437200
发表时间: 2004-05-07
影响因子: 4.8
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期刊: BIOCHIMICA ET BIOPHYSICA ACTA
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发表时间: 2005-09-01
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发表时间: 2005-02-01
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