Circular RNA CircCDH13 contributes to the pathogenesis of osteoarthritis via CircCDH13/miR-296-3p/PTEN axis
Circular RNA CircCDH13 contributes to the pathogenesis of osteoarthritis via CircCDH13/miR-296-3p/PTEN axis
复制标题
环状 RNA CircCDH13 通过 CircCDH13/miR-296-3p/PTEN 轴参与骨关节炎的发病机制。
DOI：
10.1002/jcp.30091
复制
发表时间：
2020-10-09
影响因子：
5.6
通讯作者：
Zhu, Lei
中科院分区：
文献类型：
--
作者：
Zhou, Zhibin;Ma, Jun;Zhu, Lei
环状RNA（circRNA）参与多种人类疾病;然而，circRNA在骨关节炎（OA）中的功能在很大程度上仍然未知。在这项研究中，我们研究了CircCDH 13在OA中的作用及其潜在机制。采用基因芯片技术检测OA和正常软骨组织中CircRNA的表达谱。在体外和体内研究了CircCDH 13在OA中的表达模式、功能作用和机制。使用功能获得和功能丧失方法来证明CircCDH 13在OA中的参与。通过生物信息学方法预测了CircCDH 13与miR-296- 3 p、miR-296 - 3 p与磷酸酶和张力蛋白同源物（phosphatase and tensin homolog，PTEN）的调控关系，并通过RNA pulldown和荧光素酶检测进行了验证。还使用腺相关病毒来揭示CircCDH 13在内侧半月板（DMM）诱导的OA小鼠的不稳定中的作用和机制。在OA软骨组织中，CircCDH 13的上调显著诱导软骨细胞凋亡，促进细胞外基质（ECM）的活化，并抑制ECM的活化。从机制上讲，CircCDH 13通过充当miR-296- 3 p的海绵并调节miR-296- 3 p-PTEN途径而促成OA发病机制。CircCDH 13在体内的沉默显著减轻小鼠中DMM诱导的OA。我们的研究揭示了CircCDH 13在OA发病机制中的重要作用。沉默CircCDH 13可减少软骨细胞凋亡，抑制ECM增殖，并通过miR-296- 3 p-PTEN途径促进ECM增殖。它为开发治疗OA的有效干预措施提供了潜在目标。
Circular RNAs (circRNAs) are involved in a variety of human diseases; however, the function of circRNAs in osteoarthritis (OA) remains largely unknown. In this study, we investigated the role of CircCDH13 in OA and its underlying mechanisms. CircRNA expression profiles in OA and normal cartilage tissues were detected by microarray. The expression pattern, functional role, and mechanisms of CircCDH13 in OA were studied in vitro and in vivo. Gain-of-function and loss-of-function approaches were used to demonstrate the participation of CircCDH13 in OA. The regulatory relationship between CircCDH13 and miR-296-3p and miR-296-3p and phosphatase and tensin homolog (PTEN) was predicted by bioinformatics and verified by RNA pulldown and luciferase assay. Adeno-associated virus was also used to reveal the role and mechanisms of CircCDH13 in destabilization of medial meniscus (DMM)-induced OA mice. The upregulation of CircCDH13 in OA cartilage tissues significantly induces chondrocyte apoptosis, promotes extracellular matrix (ECM) catabolism, and inhibits ECM anabolism. Mechanistically, CircCDH13 contributes to OA pathogenesis by functioning as a sponge of miR-296-3p and regulating the miR-296-3p-PTEN pathway. Silencing of CircCDH13 in vivo markedly alleviated DMM-induced OA in mice. Our study revealed an important role of CircCDH13 in OA pathogenesis. Silencing of CircCDH13 could reduce chondrocyte apoptosis, inhibit ECM catabolism, and promote ECM anabolism through the miR-296-3p-PTEN pathway. It provides a potential target for developing effective interventions in treating OA.