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胫骨轴向负荷对创伤后膝关节软骨的抗炎作用。

Anti-inflammatory effects of tibial axial loading on knee articular cartilage post traumatic injury.

作者信息

Hazbun Larry, Martinez Jose A, Best Thomas M, Kaplan Lee, Huang Chun-Yuh

机构信息

Department of Biomedical Engineering, College of Engineering, University of Miami, Coral Gables, FL, USA.

Department of Biomedical Engineering, College of Engineering, University of Miami, Coral Gables, FL, USA; Department of Orthopaedics, University of Miami Miller School of Medicine, Miami, FL, USA; UHealth Sports Medicine Institute, University of Miami, Miami, FL, USA.

出版信息

J Biomech. 2021 Nov 9;128:110736. doi: 10.1016/j.jbiomech.2021.110736. Epub 2021 Sep 6.

DOI:10.1016/j.jbiomech.2021.110736
PMID:34537673
Abstract

Early therapeutic intervention to mitigate inflammatory responses following joint injury may offer a potential strategy to prevent post-traumatic osteoarthritis (PTOA). In-vitro studies have demonstrated uniaxial dynamic compression mitigates the catabolic and apoptotic responses of articular cartilage (AC) in response to mechanical injury. The objectives of this study were (1) to develop a custom device that can apply dynamic tibial axial loading (TAL) to knee AC by mimicking therapeutic, in-vitro loading conditions and (2) to investigate the potential of TAL to reduce the inflammatory response of AC post traumatic acute joint injury using an ex-vivo porcine model. A TAL device was fabricated to apply dynamic compressive loading to knee AC by combining tibial axial compressive loading with continuous passive motion. Computational analyses demonstrated that the loading condition applied to the knee by the TAL device closely simulate uniaxial dynamic compression reported in previous in-vitro studies. Following single impact injury, injured porcine knees were subjected to TAL with a magnitude of 1/4 body weight at a frequency of 1 Hz for 30 min. AC samples were harvested 8 h post injury for analysis of pro-inflammatory cytokine expression (IL-1β and TNF-α). Expression of both cytokines was upregulated following injury; however, the change was notably mitigated in the specimens subjected to TAL. Thus, TAL may be an effective and potentially, practical-to-administer early intervention strategy to mitigate rapidly occurring detrimental events following acute AC injury, potentially slowing down progression to PTOA.

摘要

早期进行治疗性干预以减轻关节损伤后的炎症反应,可能为预防创伤后骨关节炎(PTOA)提供一种潜在策略。体外研究表明,单轴动态压缩可减轻关节软骨(AC)对机械损伤的分解代谢和凋亡反应。本研究的目的是:(1)开发一种定制装置,通过模拟治疗性体外加载条件,对膝关节AC施加动态胫骨轴向负荷(TAL);(2)使用离体猪模型研究TAL减轻创伤性急性关节损伤后AC炎症反应的潜力。通过将胫骨轴向压缩负荷与持续被动运动相结合,制造了一种TAL装置,用于对膝关节AC施加动态压缩负荷。计算分析表明,TAL装置施加于膝关节的负荷条件与先前体外研究中报道的单轴动态压缩密切相似。单次撞击损伤后,对受伤的猪膝关节施加大小为1/4体重、频率为1 Hz的TAL,持续30分钟。在损伤后8小时采集AC样本,分析促炎细胞因子表达(IL-1β和TNF-α)。损伤后两种细胞因子的表达均上调;然而,在接受TAL的标本中,这种变化明显减轻。因此,TAL可能是一种有效且可能易于实施的早期干预策略,可减轻急性AC损伤后迅速发生的有害事件,可能减缓向PTOA的进展。

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Hippo-PKCζ-NFκB signaling axis: A druggable modulator of chondrocyte responses to mechanical stress.河马蛋白激酶Cζ-核因子κB信号轴:软骨细胞对机械应力反应的可药物调控因子
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