Marine Collagen Hydrolysates Downregulate the Synthesis of Pro-Catabolic and Pro-Inflammatory Markers of Osteoarthritis and Favor Collagen Production and Metabolic Activity in Equine Articular Chondrocyte Organoids.

Marine Collagen Hydrolysates Downregulate the Synthesis of Pro-Catabolic and Pro-Inflammatory Markers of Osteoarthritis and Favor Collagen Production and Metabolic Activity in Equine Articular Chondrocyte Organoids.
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DOI:
10.3390/ijms22020580
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发表时间:
2021-01-08
影响因子:
5.6
通讯作者:
Galéra P
Galéra P
中科院分区:
生物学2区
文献类型:
--
作者:
Bourdon B;Contentin R;Cassé F;Maspimby C;Oddoux S;Noël A;Legendre F;Gruchy N;Galéra P

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关节软骨经历机械约束,导致不可避免地演变成骨关节炎(OA)的软骨缺损,因为软骨具有差的内在修复能力。虽然OA是一种无法治愈的退行性疾病,但几种膳食补充剂可能有助于改善OA的结果。在这项研究中,我们研究了Dielen®水解鱼胶原蛋白(来自皮肤(Promerim®30和Promerim®60)和软骨(Promerim®40))的作用,以分析作为类器官培养的马关节软骨细胞(eAC)的表型和代谢。在此,我们的发现证明了在生理氧下Promerim®水解物对EAC代谢活性的细胞毒性和有益效果的不存在;此外,Promerim®30还延迟了EAC衰老。为了评估Promerim®在软骨样组织中的作用,在有或没有BMP-2和/或IL-1β的情况下,将eAC在缺氧下培养为类器官。在一些情况下,单独或在IL-1β的存在下,Promerim®30和Promerim®40增加I型和II型胶原蛋白的蛋白质合成,同时降低参与OA发病机制的蛋白酶(即Htra 1)和金属蛋白酶Mmp 1 -3、Adamts 5和Cox 2的转录水平。两种Promerim®水解物也降低了Htra 1蛋白的量,特别是在炎症条件下。Promerim®的作用在炎症条件下增强,可能是由于炎症相关分子的合成减少。最后,通过增加细胞增殖或迁移,Promerim®有利于划痕伤口测定中的体外修复。总之,这些数据表明,Promerim®30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。
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 (Promerim®30 and Promerim®60) and cartilage (Promerim®40) 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, Promerim®30 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, Promerim®30 and Promerim®40 increased protein synthesis of collagen types I and II, while decreasing transcript levels of proteases involved in OA pathogenesis, namely Htra1, and the metalloproteinases Mmp1-3, Adamts5, and Cox2. 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 Promerim®30 and 40 hold promise as dietary supplements to relieve OA symptoms in patients and to delay OA progression.
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