Using Microphysiological System for the Development of Treatments for Joint Inflammation and Associated Cartilage Loss-A Pilot Study.
Using Microphysiological System for the Development of Treatments for Joint Inflammation and Associated Cartilage Loss-A Pilot Study.
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DOI：
10.3390/biom13020384
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发表时间：
2023-02-17
期刊：
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
骨关节炎(OA)是一种疼痛和致残性的关节疾病，影响着全球数百万人。缺乏临床相关模型限制了我们在临床试验之前预测治疗结果的能力，而大多数药物在临床试验中都失败了。因此，需要一种模型来准确地概括人类骨性关节炎的全关节疾病的本质。新兴的微生理系统提供了一个新的机会。我们最近建立了一个名为微型关节的微型膝关节系统，其中人骨髓间充质干细胞(HBMSCs)被用来创造骨软骨复合体、滑膜样纤维组织和脂肪组织类似物。在这项研究中，我们通过验证抗炎和软骨诱导剂联合治疗可以抑制关节炎症和相关软骨退化的假设，探索了微型关节在开发治疗OA的新方法方面的潜力。具体地说，我们通过用白细胞介素1β(IL-1β)处理滑膜样组织来建立小关节滑膜炎相关的骨关节炎模型，然后介绍了抑制核因子-κB(核因子-骨形态发生蛋白-7)遗传途径的寡脱氧核苷酸(ODN)的联合治疗。BMP-7和ODNS的联合治疗减少了滑膜样纤维组织中的炎症，并显示骨软骨复合体的软骨部分糖胺多糖的形成增加。这项研究首次证明了微型关节在开发治疗骨性关节炎的药物方面的潜力。联合应用核因子-骨形态发生蛋白B寡核苷酸和骨形态发生蛋白-7的治疗效果可在未来的临床研究中得到进一步验证。
Osteoarthritis (OA) is a painful and disabling joint disease affecting millions worldwide. The lack of clinically relevant models limits our ability to predict therapeutic outcomes prior to clinical trials, where most drugs fail. Therefore, there is a need for a model that accurately recapitulates the whole-joint disease nature of OA in humans. Emerging microphysiological systems provide a new opportunity. We recently established a miniature knee joint system, known as the miniJoint, in which human bone-marrow-derived mesenchymal stem cells (hBMSCs) were used to create an osteochondral complex, synovial-like fibrous tissue, and adipose tissue analogs. In this study, we explored the potential of the miniJoint in developing novel treatments for OA by testing the hypothesis that co-treatment with anti-inflammation and chondroinducing agents can suppress joint inflammation and associated cartilage degradation. Specifically, we created a “synovitis”-relevant OA model in the miniJoint by treating synovial-like tissues with interleukin-1β (IL-1β), and then a combined treatment of oligodeoxynucleotides (ODNs) suppressing the nuclear factor kappa beta (NF-κB) genetic pathway and bone morphogenic protein-7 (BMP-7) was introduced. The combined treatment with BMP-7 and ODNs reduced inflammation in the synovial-like fibrous tissue and showed an increase in glycosaminoglycan formation in the cartilage portion of the osteochondral complex. For the first time, this study demonstrated the potential of the miniJoint in developing disease-modifying OA drugs. The therapeutic efficacy of co-treatment with NF-κB ODNs and BMP-7 can be further validated in future clinical studies.
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