Normandie University, UNICAEN, BIOTARGEN, 14000 Caen, France.
Dielen Laboratory, 50110 Tourlaville, France.
Int J Mol Sci. 2021 Jan 8;22(2):580. doi: 10.3390/ijms22020580.
Articular cartilage experiences mechanical constraints leading to chondral defects that inevitably evolve into osteoarthritis (OA), because cartilage has poor intrinsic repair capacity. Although OA is an incurable degenerative disease, several dietary supplements may help improve OA outcomes. In this study, we investigated the effects of Dielen hydrolyzed fish collagens from skin (Promerim30 and Promerim60) and cartilage (Promerim40) to analyze the phenotype and metabolism of equine articular chondrocytes (eACs) cultured as organoids. Here, our findings demonstrated the absence of cytotoxicity and the beneficial effect of Promerim hydrolysates on eAC metabolic activity under physioxia; further, Promerim30 also delayed eAC senescence. To assess the effect of Promerim in a cartilage-like tissue, eACs were cultured as organoids under hypoxia with or without BMP-2 and/or IL-1β. In some instances, alone or in the presence of IL-1β, Promerim30 and Promerim40 increased protein synthesis of collagen types I and II, while decreasing transcript levels of proteases involved in OA pathogenesis, namely , and the metalloproteinases , and . Both Promerim hydrolysates also decreased Htra1 protein amounts, particularly in inflammatory conditions. The effect of Promerim was enhanced under inflammatory conditions, possibly due to a decrease in the synthesis of inflammation-associated molecules. Finally, Promerim favored in vitro repair in a scratch wound assay through an increase in cell proliferation or migration. Altogether, these data show that Promerim30 and 40 hold promise as dietary supplements to relieve OA symptoms in patients and to delay OA progression.
关节软骨受到力学限制,导致软骨缺陷,不可避免地发展为骨关节炎(OA),因为软骨自身修复能力差。虽然 OA 是一种不可治愈的退行性疾病,但一些膳食补充剂可能有助于改善 OA 结局。在这项研究中,我们研究了来自皮肤(Promerim30 和 Promerim60)和软骨(Promerim40)的鱼胶原蛋白水解物(Dielen)对培养为类器官的马关节软骨细胞(eAC)表型和代谢的影响。在这里,我们的研究结果表明,Promerim 水解物在低氧条件下对 eAC 代谢活性无细胞毒性作用,并且具有有益作用;此外,Promerim30 还可延缓 eAC 衰老。为了评估 Promerim 在软骨样组织中的作用,eAC 在低氧条件下培养为类器官,存在或不存在 BMP-2 和/或 IL-1β。在某些情况下,Promerim30 和 Promerim40 单独或在存在 IL-1β 的情况下,增加了 I 型和 II 型胶原的蛋白质合成,同时降低了 OA 发病机制中涉及的蛋白酶的转录水平,即 和 ,以及金属蛋白酶 和 。两种 Promerim 水解物还降低了 Htra1 蛋白含量,尤其是在炎症条件下。在炎症条件下,Promerim 的作用增强,可能是由于与炎症相关的分子合成减少。最后,Promerim 通过增加细胞增殖或迁移,在划痕伤口试验中促进体外修复。总之,这些数据表明,Promerim30 和 40 有望作为膳食补充剂,缓解患者的 OA 症状并延缓 OA 进展。
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