School of Computing, Engineering and Mathematics, University of Brighton, Cockcroft Building, Lewes Road, Brighton, BN2 4GJ, UK; School of Pharmacy and Biomolecular Sciences, University of Brighton, Huxley Building, Lewes Road, Brighton, BN2 4GJ, UK.
School of Pharmacy and Biomolecular Sciences, University of Brighton, Huxley Building, Lewes Road, Brighton, BN2 4GJ, UK; Centre for Stress and Age-related Disease, University of Brighton, Huxley Building, Lewes Road, Brighton, BN2 4GJ, UK.
Osteoarthritis Cartilage. 2020 Aug;28(8):1007-1019. doi: 10.1016/j.joca.2020.03.021. Epub 2020 May 21.
In previous research the use of hydrostatic pressure (HP) has been applied to enhance the formation of engineered cartilage, through the up-regulation of proteoglycan synthesis by mechanotransduction. However, the HP stimulation approach has been shown to vary between studies with a wide disparity in results, including anabolic, catabolic and non-responsive outcomes. To this end, a meta-analysis of HP publications using 3D cultured chondrocytes was performed to elucidate the key experiment factors involved in achieving a mechanotransducive response.
The effects of different HP regimes on proteoglycan production were investigated based on the following factors: static vs dynamic application, pressure magnitude, and experiment duration. Meta-analysis was performed on raw data taken from 11 publications which employed either aggrecan gene expression analysis or dimethyl methylene blue colorimetric assay. The measure of effect was calculated based on mean difference using a random effects model.
Analysis revealed that a significant anabolic response was most likely achieved when the following factors were employed; a static HP application, a magnitude within the mid-high physiological range of cartilage (≤5-10 MPa) and a study duration of ≥2 weeks.
Thus, we propose that the selection of HP experiment factors can have a significant influence on engineered cartilage development, and that the results of this meta-analysis can be used as a basis for the planning of future HP experiments.
在之前的研究中，通过机械转导增加蛋白聚糖合成，已经应用流体静压力 (HP) 来增强工程软骨的形成。然而，HP 刺激方法在研究之间存在差异，结果差异很大，包括合成代谢、分解代谢和无应答的结果。为此，对使用三维培养软骨细胞的 HP 出版物进行了荟萃分析，以阐明实现机械转导反应所涉及的关键实验因素。
根据以下因素研究不同 HP 方案对蛋白聚糖产生的影响：静态与动态应用、压力大小和实验持续时间。对采用聚集蛋白聚糖基因表达分析或二甲亚甲基蓝比色测定法的 11 篇出版物中的原始数据进行荟萃分析。使用随机效应模型，根据均数差值计算效应量。
分析表明，当采用以下因素时，很可能获得显著的合成代谢反应：静态 HP 应用、处于软骨的中高生理范围（≤5-10 MPa）内的压力大小以及≥2 周的研究持续时间。
因此，我们提出 HP 实验因素的选择会对工程软骨的发育产生重大影响，并且可以将此荟萃分析的结果作为未来 HP 实验规划的基础。
