circRNA-miRNA网络调控骨重塑的研究进展
Research Progress in the Regulatory Role of circRNA-miRNA Network in Bone Remodeling
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摘要: 骨形成与骨吸收的动态平衡是骨重塑的重要过程。骨形成和骨吸收的失调与多种骨相关疾病的发生发展密切相关。非编码RNA(noncoding RNA, ncRNA)通过抑制mRNA翻译或降解mRNA,在生理和病理条件下对蛋白质的表达起调控作用。环状RNA(circular RNA, circRNA)是一种非线性ncRNA,能抵御RNA外切酶的降解作用。circRNA和微RNA(microRNA, miRNA)可直接或间接调控成骨相关基因的表达,从而在骨重塑过程中发挥重要作用。研究证实circRNA-miRNA网络参与间充质干细胞(mesenchymal stem cells, MSCs)向成骨细胞(osteoblasts, OB)谱系分化过程,也参与了骨髓来源巨噬细胞(bone marrow-derived macrophages, BMDM)向破骨细胞(osteoclasts, OC)分化的过程,在骨重塑的成骨-破骨平衡中起重要调节作用。因此,充分了解circRNA-miRNA调控网络将有助于理解骨重塑过程中的成、破骨平衡的调节机制和相关疾病的诊断和治疗。本文就circRNA、microRNA的功能及其作为circRNA-miRNA调控网络机制在骨重塑过程中作用进行综述,以期为今后深入理解骨重塑调控机制和相关疾病的研究和防治提供参考和思路。Abstract: The dynamic balance between bone formation and bone resorption is a critical process of bone remodeling. The imbalance of bone formation and bone resorption is closely associated with the occurrence and development of various bone-related diseases. Under both physiological and pathological conditions, non-coding RNAs (ncRNAs) play a crucial regulatory role in protein expression through either inhibiting mRNAs translation or promoting mRNAs degradation. Circular RNAs (circRNAs) are a type of non-linear ncRNAs that can resist the degradation of RNA exonucleases. There is accumulating evidence suggesting that circRNAs and microRNAs (miRNAs) serve as critical regulators of bone remodeling through their direct or indirect regulation of the expression of osteogenesis-related genes. Additionally, recent studies have revealed the involvement of the circRNAs-miRNAs regulatory network in the process by which mesenchymal stem cells (MSCs) differentiate towards the osteoblasts (OB) lineage and the process by which bone marrow-derived macrophages (BMDM) differentiate towards osteoclasts (OC). The circRNA-miRNA network plays an important regulatory role in the osteoblastic-osteoclastic balance of bone remodeling. Therefore, a thorough understanding of the circRNA-miRNA regulatory mechanisms will contribute to a better understanding of the regulatory mechanisms of the balance between osteoblastic and osteoclastic activities in the process of bone remodeling and the diagnosis and treatment of related diseases. Herein, we reviewed the functions of circRNA and microRNA. We also reviewed their roles in and the mechanisms of the circRNA-miRNA regulatory network in the process of bone remodeling. This review provides references and ideas for further research on the regulation of bone remodeling and the prevention and treatment of bone-related diseases.