Circular RNAs as potential regulators in bone remodeling: a narrative review

Objective: In this review, we focus on the recent progress of circular ribonucleic acids (circRNAs)-related molecular mechanisms in the processes of osteogenesis and osteoclastogenesis, and explore their roles in the development of bone-remodeling disorders. Background: The well-coupled bone-formation and bone-resorption processes are vital in bone remodeling. Once the balance is disrupted, bone-remodeling disorders (e.g., osteoporosis and osteopetrosis) occur, severely affecting patients' quality of life. CircRNAs, the newly discovered members of the non coding RNA family, have been reported to act as key checkpoints of various signaling pathways that influence osteoblasts and osteoclasts functions, thus regulating the physiological and pathological processes of bone homeostasis. Methods: Three English and three Chinese databases [i.e., PubMed, Embase, MEDLINE (via Ovid), Chinese Biomedical Literature, China National Knowledge Infrastructure, and VIP databases] were searched to June 2021 without language restrictions. Studies exploring the roles of circRNAs in key bone remodeling mediators, such as Smad-dependent bone morphogenetic protein (BMP)/transforming growth factor beta (TGF-beta), Wnts, runt-related transcription factor (RUNX), forkhead boxes (FOXs), colony-stimulating factor 1 (CSF-1), receptor activator of nuclear factor kappa B ligand (RANKL)/osteoprotegerin (OPG), and circRNA-related bone-remodeling disorders, were included. Conclusions: Many circRNAs have been shown to promote osteogenesis and facilitate osteoclast differentiation via diverse mechanisms, and thus modulate the process of bone homeostasis. The imbalance or impairment of these two parts causes diseases, such as osteoporosis, and osteonecrosis of the femoral head, which are also closely correlated to the aberrant presence of circRNAs. Current evidence provides us with promising diagnosis and treatment methods for some bone homeostasis disorders.