The role of long non‐coding RNAs and circular RNAs in bone regeneration: Modulating miRNAs function

Although bone is a self-healing organ and is able to repair and restore most fractures, large bone fractures, about 10%, are not repairable. Bone grafting, as a gold standard, and bone tissue engineering using biomaterials, growth factors, and stem cells have been developed to restore large bone defects. Since bone regeneration is a complex and multiple-step process and the majority of the human genome, about 98%, is composed of the non-protein-coding regions, non-coding RNAs (ncRNAs) play essential roles in bone regeneration. Recent studies demonstrated that long ncRNAs (lncRNAs) and circular RNAs (circRNAs), as members of ncRNAs, are widely involved in bone regeneration by interaction with microRNAs (miRNAs) and constructing a lncRNA or circRNA/miRNA/mRNA regulatory network. The constructed network regulates the differentiation of stem cells into osteoblasts and their commitment to osteogenesis. This review will present the structure and biogenesis of lncRNAs and circRNAs, the mechanism of bone repair, and the bone tissue engineering in bone defects. Finally, we will discuss the role of lncRNAs and circRNAs in osteogenesis and bone fracture healing through constructing various lncRNA or circRNA/miRNA/mRNA networks and the involved pathways.