Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100144, PR China.
Int J Biol Sci. 2023 May 21;19(9):2740-2755. doi: 10.7150/ijbs.83024. eCollection 2023.
Elastic cartilage tissue engineering is promising for providing available scaffolds for plastic reconstructive surgery. The insufficient mechanical strength of regenerative tissue and scarce resources of reparative cells are two obstacles for the preparation of tissue-engineered elastic cartilage scaffolds. Auricular chondrocytes are important reparative cells for elastic cartilage tissue engineering, but resources are scarce. Identifying auricular chondrocytes with enhanced capability of elastic cartilage formation is conducive to reducing the damage to donor sites by decreasing the demand on native tissue isolation. Based on the biochemical and biomechanical differences in native auricular cartilage, we found that auricular chondrocytes with upregulated desmin expressed more integrin β1, forming a stronger interaction with the substrate. Meanwhile, activated MAPK pathway was found in auricular chondrocytes highly expressing desmin. When desmin was knocked down, the chondrogenesis and mechanical sensitivity of chondrocytes were both impaired, and the MAPK pathway was downregulated. Finally, auricular chondrocytes highly expressing desmin regenerated more elastic cartilage with increased ECM mechanical strength. Therefore, desmin/integrin β1/MAPK signaling can not only serve as a selection standard but also a manipulation target of auricular chondrocytes to promote elastic cartilage regeneration.
弹性软骨组织工程有望为整形重建外科提供可用的支架。再生组织的机械强度不足和修复细胞的资源匮乏是组织工程弹性软骨支架制备的两个障碍。耳软骨细胞是弹性软骨组织工程的重要修复细胞，但资源稀缺。鉴定具有增强弹性软骨形成能力的耳软骨细胞有利于通过减少对固有组织分离的需求来减少对供体部位的损伤。基于天然耳软骨的生化和生物力学差异，我们发现上调表达结蛋白的耳软骨细胞表达更多的整合素β1，与基质形成更强的相互作用。同时，在高表达结蛋白的耳软骨细胞中发现激活的 MAPK 通路。当结蛋白被敲低时，软骨细胞的软骨生成和力学敏感性都受到损害，MAPK 通路被下调。最后，高表达结蛋白的耳软骨细胞再生出具有更高 ECM 机械强度的更多弹性软骨。因此，结蛋白/整合素β1/MAPK 信号不仅可以作为耳软骨细胞的选择标准，也可以作为促进弹性软骨再生的操作靶点。
