Hyperphysiological compression of articular cartilage induces an osteoarthritic phenotype in a cartilage-on-a-chip model
Hyperphysiological compression of articular cartilage induces an osteoarthritic phenotype in a cartilage-on-a-chip model
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DOI：
10.1038/s41551-019-0406-3
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发表时间：
2019-07-01
影响因子：
28.1
通讯作者：
Rasponi, Marco
中科院分区：
文献类型：
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作者：
Occhetta, Paola;Mainardi, Andrea;Rasponi, Marco
由于人口老龄化，骨关节炎（OA）-最常见的肌肉骨骼疾病-的社会影响预计将急剧增加。然而，治疗仍然局限于姑息治疗或手术干预，疾病修饰OA（DMOA）药物稀缺，主要是因为缺乏相关的临床前OA模型。因此，需要能够可靠地预测DMOA药物功效的体外模型。在这里，我们表明，使用一个新开发的微生理软骨芯片模型，使应变控制压缩三维关节软骨微组织的应用程序，30%的限制压缩概括了OA发病机制中涉及的机械因素，足以诱导OA性状。这种超生理性压迫触发软骨稳态向软骨炎和炎症、肥大的转变，并获得与临床骨关节炎组织中所见相似的基因表达谱。软骨芯片模型可以实现DMOA候选物的筛选。
Owing to population aging, the social impact of osteoarthritis (OA)-the most common musculoskeletal disease-is expected to increase dramatically. Yet, therapy is still limited to palliative treatments or surgical intervention, and disease-modifying OA (DMOA) drugs are scarce, mainly because of the absence of relevant preclinical OA models. Therefore, in vitro models that can reliably predict the efficacy of DMOA drugs are needed. Here, we show, using a newly developed microphysiological cartilage-on-a-chip model that enables the application of strain-controlled compression to three-dimensional articular cartilage microtissue, that a 30% confined compression recapitulates the mechanical factors involved in OA pathogenesis and is sufficient to induce OA traits. Such hyperphysiological compression triggers a shift in cartilage homeostasis towards catabolism and inflammation, hypertrophy, and the acquisition of a gene expression profile akin to those seen in clinical osteoarthritic tissue. The cartilage on-a-chip model may enable the screening of DMOA candidates.