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Macrophage-activating lipoprotein (MALP)-2 impairs the healing of partial tendon injuries in mice
Annals of Anatomy ( IF 2.2 ) Pub Date : 2021-08-13 , DOI: 10.1016/j.aanat.2021.151818
Tobias Fritz 1 , Julia Schäfer 1 , Claudia Scheuer 2 , Janine Stutz 1 , Tina Histing 3 , Tim Pohlemann 1 , Michael D Menger 2 , Matthias W Laschke 2 , Moritz Klein 1 , Marcel Orth 1
Affiliation  

Tendon injuries are accounted for up to 50% of musculoskeletal injuries and often result in poor outcomes. Inflammation is a major hallmark of tendon regeneration. Therefore, we analyzed in this study whether the topical application of the pro-inflammatory mediator macrophage-activating lipoprotein (MALP)-2 improves the healing of partial tendon injuries. C57BL/6 mice underwent a partial tenotomy of the flexor digitorum longus tendon of the left hind limb, which was treated with a solution containing either 0.5 µg MALP-2 or vehicle (control). Repetitive gait analyses were performed prior to the surgical intervention as well as postoperatively on days 1, 3, 7, 14 and 36. The structural stability of the tendons was biomechanically tested on day 7 and 36. In addition, Western blot analyses were performed on isolated tendons that were treated in vitro with MALP-2 or vehicle. In both groups, partial tenotomy resulted in a pathological gait pattern during the initial postoperative phase. On day 7, the gait pattern normalized in vehicle-treated animals, but not in MALP-2-treated mice. Moreover, the tendons of MALP-2-treated mice exhibited a significantly reduced biomechanical stiffness after 7 and 36 days when compared to controls. Western blot analyses revealed a significantly higher expression of heme oxygenase (HO)-1 and lower expression of cyclin D in MALP-2-treated tendons. These findings indicate that MALP-2 delays the healing of injured tendons most likely due to increased intracellular stress and suppressed cell proliferation in this naturally bradytrophic tissue. Hence, the application of MALP-2 cannot be recommended for the treatment of tendon injuries.



中文翻译:

巨噬细胞激活脂蛋白 (MALP)-2 损害小鼠部分肌腱损伤的愈合

肌腱损伤占肌肉骨骼损伤的 50%,通常会导致不良结果。炎症是肌腱再生的主要标志。因此,我们在本研究中分析了局部应用促炎介质巨噬细胞活化脂蛋白 (MALP)-2 是否能改善部分肌腱损伤的愈合。C57BL/6 小鼠接受了左后肢趾长屈肌腱的部分肌腱切断术,用含有 0.5 µg MALP-2 或载体(对照)的溶液处理。在手术干预之前以及术后第 1、3、7、14 和 36 天进行了重复步态分析。在第 7 天和第 36 天对肌腱的结构稳定性进行了生物力学测试。此外,对体外用 MALP-2 或载体处理的分离肌腱进行蛋白质印迹分析。在两组中,部分肌腱切断术在术后初始阶段导致病理性步态模式。在第 7 天,在载体处理的动物中步态模式正常化,但在 MALP-2 处理的小鼠中未正常化。此外,与对照组相比,MALP-2 治疗小鼠的肌腱在 7 天和 36 天后表现出显着降低的生物力学刚度。蛋白质印迹分析显示,在 MALP-2 处理的肌腱中,血红素加氧酶 (HO)-1 的表达显着升高,细胞周期蛋白 D 的表达显着降低。这些发现表明,MALP-2 延迟了受伤肌腱的愈合,这很可能是由于细胞内压力增加并抑制了这种自然发育迟缓组织中的细胞增殖。因此,

更新日期:2021-08-21
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