Shearing of synovial fluid activates latent TGF-β
Shearing of synovial fluid activates latent TGF-β
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DOI：
10.1016/j.joca.2012.07.006
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发表时间：
2012-11-01
影响因子：
7
通讯作者：
Ateshian, G. A.
中科院分区：
文献类型：
--
作者：
Albro, M. B.;Cigan, A. D.;Ateshian, G. A.
目的：TGF-β在无活性的潜伏复合物中合成，该复合物不能与膜受体结合，因此在其被激活之前不能诱导细胞生物学应答。除了通过化学介质激活之外，最近的研究已经证明，机械力可以通过整合素介导的细胞收缩或血清的机械剪切来激活潜伏的TGF-β。由于TGF-β以潜伏形式存在于滑液中，并且由于正常的关节功能产生流体剪切，因此本研究测试了滑液中的天然潜伏TGF-β 1可以通过剪切激活的假设。设计：来自26个牛关节和3个成人关节的滑液在平均剪切速率高达4000 s（-1）下剪切长达15 h。发现未剪切的滑液含有高水平的潜伏性TGF-β 1（4.35 +/- 2.02 ng/mL牛，1.84 +/- 0.89 ng/mL人; 95%置信区间的平均值+/-半径）和低量（< 0.05 ng/mL）的活性肽。滑液中活性TGF-β 1的浓度随剪切速率和剪切持续时间单调增加，牛滑液达到2.64 +/- 1.22 ng/mL，人滑液达到0.60 +/- 0.39 ng/mL。剪切终止后，在接下来的8小时内，两种物质的这些活性水平均无统计学变化，证明了活化肽的长期稳定性。unsheared对照组继续表现出可忽略不计的活性TGF-β 1的水平在所有times.Conclusions：结果证实了本研究的假设，并建议剪切滑液可能有助于diarthodial关节的机械负荷的额外的生物合成效果。(C)2012年国际骨关节炎研究学会。由爱思唯尔有限公司出版。保留所有权利。
Objective: TGF-beta is synthesized in an inactive latent complex that is unable to bind to membrane receptors, thus unable to induce a cellular biological response until it has been activated. In addition to activation by chemical mediators, recent studies have demonstrated that mechanical forces may activate latent TGF-beta via integrin-mediated cellular contractions, or mechanical shearing of blood serum. Since TGF-beta is present in synovial fluid in latent form, and since normal diarthrodial joint function produces fluid shear, this study tested the hypothesis that the native latent TGF-beta 1 of synovial fluid can be activated by shearing.Design: Synovial fluid from 26 bovine joints and three adult human joints was sheared at mean shear rates up to 4000 s(-1) for up to 15 h.Results: Unsheared synovial fluid was found to contain high levels of latent TGF-beta 1 (4.35 +/- 2.02 ng/mL bovine, 1.84 +/- 0.89 ng/mL human; mean +/- radius of 95% confidence interval) and low amounts (< 0.05 ng/mL) of the active peptide. Synovial fluid concentrations of active TGF-beta 1 increased monotonically with shear rate and shearing duration, reaching levels of 2.64 +/- 1.22 ng/mL for bovine and 0.60 +/- 0.39 ng/mL for human synovial fluid. Following termination of shearing, there was no statistical change in these active levels over the next 8 h for either species, demonstrating long-term stability of the activated peptide. The unsheared control group continued to exhibit negligible levels of active TGF-beta 1 at all times.Conclusions: Results confirmed the hypothesis of this study and suggest that shearing of synovial fluid might contribute an additional biosynthetic effect of mechanical loading of diarthrodial joints. (C) 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.