Functionalized Nanogels with Endothelin-1 and Bradykinin Receptor Antagonist Peptides Decrease Inflammatory and Cartilage Degradation Markers of Osteoarthritis in a Horse Organoid Model of Cartilage.
Functionalized Nanogels with Endothelin-1 and Bradykinin Receptor Antagonist Peptides Decrease Inflammatory and Cartilage Degradation Markers of Osteoarthritis in a Horse Organoid Model of Cartilage.
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DOI：
10.3390/ijms23168949
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发表时间：
2022-08-11
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
骨关节炎（OA）是一种退行性和异质性疾病，影响所有类型的关节结构。目前的临床治疗只是对症治疗，不能控制动物或人类的退行性过程。正在开发的用于治疗OA的新的矫形生物学治疗策略之一是使用药物递送系统（DDS）在长时间内将生物活性分子直接释放到关节中，以限制炎症，控制疼痛并减少软骨退化。两种血管活性肽，内皮素-1和缓激肽，在OA发病机制中起重要作用。在这项研究中，我们研究了两种功能化的纳米凝胶作为DDS的效果。我们评估了用A型内皮素受体拮抗剂（BQ-123-CHI）官能化的壳聚糖和/或用B1型缓激肽受体拮抗剂（R-954-HA）官能化的透明质酸的作用。这些纳米凝胶单独或组合的生物相容性首先在不同含氧条件下培养的马关节软骨细胞上得到验证。此外，在通过用白介素-1 β（IL-1β）诱导的OA马类器官模型中，BQ-123-CHI和R-954-HA（BR 5）的组合引发炎症和分解代谢标志物的最大降低。在基础和OA条件下，单独或与R-954-HA等摩尔组合的BQ-123-CHI对胶原合成具有弱的促合成代谢作用。这些新的纳米凝胶，作为复合DDS的一部分，显示出治疗OA的有前途的属性。
Osteoarthritis (OA) is a degenerative and heterogeneous disease that affects all types of joint structures. Current clinical treatments are only symptomatic and do not manage the degenerative process in animals or humans. One of the new orthobiological treatment strategies being developed to treat OA is the use of drug delivery systems (DDS) to release bioactive molecules over a long period of time directly into the joint to limit inflammation, control pain, and reduce cartilage degradation. Two vasoactive peptides, endothelin-1 and bradykinin, play important roles in OA pathogenesis. In this study, we investigated the effects of two functionalized nanogels as DDS. We assessed the effect of chitosan functionalized with a type A endothelin receptor antagonist (BQ-123-CHI) and/or hyaluronic acid functionalized with a type B1 bradykinin receptor antagonist (R-954-HA). The biocompatibility of these nanogels, alone or in combination, was first validated on equine articular chondrocytes cultured under different oxic conditions. Further, in an OA equine organoid model via induction with interleukin-1 beta (IL-1β), a combination of BQ-123-CHI and R-954-HA (BR5) triggered the greatest decrease in inflammatory and catabolic markers. In basal and OA conditions, BQ-123-CHI alone or in equimolar combinations with R-954-HA had weak pro-anabolic effects on collagens synthesis. These new nanogels, as part of a composite DDS, show promising attributes for treating OA.
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影响因子：
4.9
作者：
Kaufman GN;Zaouter C;Valteau B;Sirois P;Moldovan F
通讯作者：
Moldovan F
影响因子：
3.3
作者：
Sophia Fox AJ;Bedi A;Rodeo SA
通讯作者：
Rodeo SA
影响因子：
7.3
作者：
CRUWYS, SC;GARRETT, NE;KIDD, BL
通讯作者：
KIDD, BL
骨关节炎的炎症。
影响因子：
5.1
作者：
Goldring MB;Otero M
通讯作者：
Otero M
影响因子：
5.6
作者：
Bourdon B;Contentin R;Cassé F;Maspimby C;Oddoux S;Noël A;Legendre F;Gruchy N;Galéra P
通讯作者：
Galéra P