Department of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, 230001, Hefei, Anhui, China.
Department of Hepatobiliary Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, 230001, Hefei, Anhui, China.
Exp Mol Med. 2023 Sep;55(9):2051-2066. doi: 10.1038/s12276-023-01085-y. Epub 2023 Sep 1.
The identification of key regulatory factors that control osteoclastogenesis is important. Accumulating evidence indicates that circular RNAs (circRNAs) are discrete functional entities. However, the complexities of circRNA expression as well as the extent of their regulatory functions during osteoclastogenesis have yet to be revealed. Here, based on circular RNA sequencing data, we identified a circular RNA, circFam190a, as a critical regulator of osteoclast differentiation and function. During osteoclastogenesis, circFam190a is significantly upregulated. In vitro, circFam190a enhanced osteoclast formation and function. In vivo, overexpression of circFam190a induced significant bone loss, while knockdown of circFam190a prevented pathological bone loss in an ovariectomized (OVX) mouse osteoporosis model. Mechanistically, our data suggest that circFam90a enhances the binding of AKT1 and HSP90β, promoting AKT1 stability. Altogether, our findings highlight the critical role of circFam190a as a positive regulator of osteoclastogenesis, and targeting circFam190a might be a promising therapeutic strategy for treating pathological bone loss.
鉴定控制破骨细胞形成的关键调节因子非常重要。越来越多的证据表明，环状 RNA（circRNA）是离散的功能实体。然而，circRNA 表达的复杂性及其在破骨细胞形成过程中的调节功能的程度尚未被揭示。在这里，基于环状 RNA 测序数据，我们鉴定出一个环状 RNA，circFam190a，是破骨细胞分化和功能的关键调节因子。在破骨细胞形成过程中，circFam190a 显著上调。在体外，circFam190a 增强破骨细胞的形成和功能。在体内，circFam190a 的过表达诱导了明显的骨丢失，而 circFam190a 的敲低则防止了去卵巢（OVX）小鼠骨质疏松模型中的病理性骨丢失。从机制上讲，我们的数据表明，circFam90a 增强了 AKT1 和 HSP90β 的结合，促进了 AKT1 的稳定性。总之，我们的研究结果强调了 circFam190a 作为破骨细胞形成的正调节剂的关键作用，靶向 circFam190a 可能是治疗病理性骨丢失的一种有前途的治疗策略。
