Li Jia, Shi Hang, Liu Xia, Jiang Haiyue
Plastic Surgery Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 33 Ba-da-chu Road, Shijingshan District, Beijing 100144, China.
J Tissue Eng Regen Med. 2023 May 26;2023:9985334. doi: 10.1155/2023/9985334. eCollection 2023.
Nonsyndromic microtia is a kind of congenital ear malformation with unclear pathogenic genes. Cadherin-11 (CDH11, OB-cadherin) is a member of the cadherin family, which has been demonstrated to play important roles in controlling morphogenesis and cell biological characteristics during multiple developmental processes. In the present study, we found low expression of CDH11 in microtia cartilage compared with the normal one for the first time. For a more comprehensive and in-depth understanding of CDH11 in microtia development, we performed both gain- and loss-of-function experiments to detect the effect of CDH11 on chondrocytes. CDH11 promoted chondrocyte proliferation by increasing S-phase cell numbers and increasing cell migration, which is important for tissue morphogenesis. Additionally, knockdown of CDH11 in chondrocytes reduced the quality of engineered cartilage by decreasing the key transcription factors of chondrogenesis, SOX9 expression, and cartilage ECM production, including collagen type II (COL2A) and elastin (ELN), compared to the control group. Furthermore, RNA-Seq on CDH11 knockdown chondrocytes showed that it was highly related to HOX family genes, which have been reported to be important regulatory genes patterning craniofacial tissue formation. This study identified CDH11 as a candidate pathogenic gene of microtia and supported the potential key role of CDH11 in craniofacial malformations.
非综合征性小耳畸形是一种致病基因尚不明确的先天性耳部畸形。钙黏蛋白-11（CDH11，骨桥蛋白钙黏蛋白）是钙黏蛋白家族的一员，已被证明在多个发育过程中控制形态发生和细胞生物学特性方面发挥重要作用。在本研究中，我们首次发现与正常软骨相比，小耳畸形软骨中CDH11表达较低。为了更全面、深入地了解CDH11在小耳畸形发育中的作用，我们进行了功能获得和功能丧失实验，以检测CDH11对软骨细胞的影响。CDH11通过增加S期细胞数量和促进细胞迁移来促进软骨细胞增殖，这对组织形态发生很重要。此外，与对照组相比，软骨细胞中CDH11的敲低通过降低软骨形成的关键转录因子SOX9的表达以及软骨细胞外基质（ECM）的产生，包括II型胶原蛋白（COL2A）和弹性蛋白（ELN），降低了工程化软骨的质量。此外，对CDH11敲低的软骨细胞进行RNA测序显示，它与HOX家族基因高度相关，据报道HOX家族基因是颅面组织形成模式的重要调控基因。本研究确定CDH11为小耳畸形的候选致病基因，并支持CDH11在颅面畸形中可能发挥的关键作用。
