CircFam190a: a critical positive regulator of osteoclast differentiation via enhancement of the AKT1/HSP90β complex

• Published in: Experimental & molecular medicine Vol. 55; no. 9; pp. 2051 - 2066
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2023; Springer Nature B.V; Nature Publishing Group; 생화학분자생물학회
• Subjects: 13/1; 13/107; 13/109; 13/89; 13/95; 14/105; 14/19; 14/32; 14/63; 38/39; 631/136/815/816; 64/60; 692/163/2743/316/801; 82/111; 82/58; 82/80; 96/100; AKT1 protein; Biomedical and Life Sciences; Biomedicine; Bone density; Bone diseases; Bone growth; Bone loss; Circular RNA; Gene regulation; Medical Biochemistry; Molecular Medicine; Osteoclastogenesis; Osteoclasts; Osteogenesis; Osteoporosis; Ovariectomy; Ribonucleic acid; RNA; Stem Cells; 생화학
• ISSN: 2092-6413; 1226-3613; 2092-6413
• DOI: 10.1038/s12276-023-01085-y

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. Bone disease: Circular RNA in bone formation 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.