CircFam190a: a critical positive regulator of osteoclast differentiation via enhancement of the AKT1/HSP90β complex.
CircFam190a: a critical positive regulator of osteoclast differentiation via enhancement of the AKT1/HSP90β complex.
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DOI：
10.1038/s12276-023-01085-y
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发表时间：
2023-09
影响因子：
12.8
通讯作者：
Shang, Xifu
中科院分区：
文献类型：
--
作者：
Chen, Kun;Chen, Xi;Lang, Chuandong;Yuan, Xingshi;Huang, Junming;Li, Zhi;Xu, Mingyou;Wu, Kerong;Zhou, Chenhe;Li, Qidong;Zhu, Chen;Liu, Lianxin;Shang, Xifu
识别控制破骨细胞形成的关键调控因素是很重要的。越来越多的证据表明，环状RNA(CircRNAs)是离散的功能实体。然而，CircRNA表达的复杂性以及它们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，我们确定了一个环状RNA，CircFam190a，作为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，大约FAM190a基因表达显著上调。在体外，CircFam190a可促进破骨细胞的形成和功能。在体内，在卵巢切除(OVX)的小鼠骨质疏松模型中，过表达CircFam190a导致了显著的骨丢失，而下调CircFam190a则阻止了病理性骨丢失。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。综上所述，我们的发现强调了CircFam190a作为破骨细胞形成的正向调节因子的关键作用，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。一种新发现的促进骨降解破骨细胞发育的环状RNA分子为预防骨质疏松等条件下的骨骼退化提供了一个有希望的靶点。破骨细胞在维持健康的骨密度方面起着至关重要的作用，但过度的活动会导致骨组织的侵蚀和脆弱。几项研究表明，基因调控的环状RNA在破骨细胞的发育中发挥了作用，合肥中国科技大学的陈坤和他的同事已经确定了一种名为CircFam190a的这样的分子。他们证明，靶向抑制CircFam190a可以在不干扰成骨细胞活动的情况下，在骨质疏松症小鼠模型中保持骨骼的完整性。研究人员还发现了更广泛的信号通路网络，其中包括几种在破骨细胞功能中具有明确作用的蛋白质。
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. A newly discovered circular RNA molecule that promotes development of bone-degrading osteoclast cells offers a promising target for preventing skeletal degeneration in conditions like osteoporosis. Osteoclasts play a critical role in maintaining healthy bone density but excess activity can lead to eroded and fragile bone tissue. Several studies have suggested that gene-regulating circular RNAs play a role in osteoclast development, and Kun Chen of the University of Science and Technology of China, Hefei, and colleagues have identified one such molecule called circFam190a. They demonstrate that targeted inhibition of circFam190a can preserve bone integrity in a mouse model of osteoporosis without interfering with the activity of bone-generating osteoblast cells. The authors were also able to identify the broader network of signaling pathways influenced by circFam190a, which include several proteins with well-established roles in osteoclast function.
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