Research Progress in the Regulatory Role of circRNA-miRNA Network in Bone Remodeling

LAN Yuanchen, YU Liyuan, HU Zhiai, ZOU Shujuan

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.

 

Keywords: Circular RNA,  microRNA,  Osteogenic differentiation,  Osteoclastic differentiation,  Bone remodeling,  Review

 

Full Text:

PDF


References


WAN Y. PPARγ in bone homeostasis. Trends Endocrinol Metab,2010, 21(12): 722–728. doi: 10.1016/j.tem.2010.08.006.

BOYLE W J, SIMONET W S, LACEY D L. Osteoclast differentiation and activation. Nature,2003,423(6937): 337–342. doi: 10.1038/nature01658.

FENG X, MCDONALD J M. Disorders of bone remodeling. Annu Rev Pathol,2011,6: 121–145. doi: 10.1146/annurev-pathol-011110-130203.

KIM J M, LIN C, STAVRE Z, et al. Osteoblast-osteoclast communication and bone homeostasis. Cells,2020,9(9): 2073. doi: 10. 3390/cells9092073.

ZHAO W, SHEN G, REN H, et al. Therapeutic potential of microRNAs in osteoporosis function by regulating the biology of cells related to bone homeostasis. J Cell Physiol,2018,233(12): 9191–9208. doi: 10.1002/jcp. 26939.

LI J, CHEN X, LU L, et al. The relationship between bone marrow adipose tissue and bone metabolism in postmenopausal osteoporosis. Cytokine Growth Factor Rev,2020,52: 88–98. doi: 10.1016/j.cytogfr.2020. 02.003.

SOBACCHI C, SCHULZ A, COXON F P, et al. Osteopetrosis: genetics, treatment and new insights into osteoclast function. Nat Rev Endocrinol, 2013,9(9): 522–536. doi: 10.1038/nrendo.2013.137.

DEVAUX C A, RAOULT D. The microbiological memory, an epigenetic regulator governing the balance between good health and metabolic disorders. Front Microbiol,2018,9: 1379. doi: 10.3389/fmicb.2018.01379.

CHEN Y, HONG T, WANG S, et al. Epigenetic modification of nucleic acids: from basic studies to medical applications. Chem Soc Rev,2017, 46(10): 2844–2872. doi: 10.1039/c6cs00599c.

SHARMA G, SULTANA A, ABDULLAH K M, et al. Epigenetic regulation of bone remodeling and bone metastasis. Semin Cell Dev Biol, 2024,154(Pt C): 275–285. doi: 10.1016/j.semcdb.2022.11.002.

IYER M K, NIKNAFS Y S, MALIK R, et al. The landscape of long noncoding RNAs in the human transcriptome. Nat Genet,2015,47(3): 199–208. doi: 10.1038/ng.3192.

KANG Y, GUO S, SUN Q, et al. Differential circular RNA expression profiling during osteogenic differentiation in human adipose-derived stem cells. Epigenomics,2020,12(4): 289–302. doi: 10.2217/epi-2019-0218.

ZHANG D, NI N, WANG Y, et al. CircRNA-vgll3 promotes osteogenic differentiation of adipose-derived mesenchymal stem cells via modulating miRNA-dependent integrin α5 expression. Cell Death Differ,2021,28(1): 283–302. doi: 10.1038/s41418-020-0600-6.

WANG W, QIAO S C, WU X B, et al. Circ_0008542 in osteoblast exosomes promotes osteoclast-induced bone resorption through m6A methylation. Cell Death Dis,2021,12(7): 628. doi: 10.1038/s41419-021-03915-1.

ALI S A, PEFFERS M J, ORMSETH M J, et al. The non-coding RNA interactome in joint health and disease. Nat Rev Rheumatol,2021,17(11): 692–705. doi: 10.1038/s41584-021-00687-y.

RUPAIMOOLE R, SLACK F J. MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov,2017,16(3): 203–222. doi: 10.1038/nrd.2016.246.

LUND E, GÜTTINGER S, CALADO A, et al. Nuclear export of microRNA precursors. Science,2004,303(5654): 95–98. doi: 10.1126/science.1090599.

FUKUNAGA R, HAN B W, HUNG J H, et al. Dicer partner proteins tune the length of mature miRNAs in flies and mammals. Cell,2012, 151(3): 533–546. doi: 10.1016/j.cell.2012.09.027.

FABIAN M R, SONENBERG N. The mechanics of miRNA-mediated gene silencing: a look under the hood of miRISC. Nat Struct Mol Biol, 2012,19(6): 586–593. doi: 10.1038/nsmb.2296.

KILIKEVICIUS A, MEISTER G, COREY D R. Reexamining assumptions about miRNA-guided gene silencing. Nucleic Acids Res, 2022,50(2): 617–634. doi: 10.1093/nar/gkab1256.

JONAS S, CHRISTIE M, PETER D, et al. An asymmetric PAN3 dimer recruits a single PAN2 exonuclease to mediate mRNA deadenylation and decay. Nat Struct Mol Biol,2014,21(7): 599–608. doi: 10.1038/nsmb.2837.

YING W, RIOPEL M, BANDYOPADHYAY G, et al. Adipose tissue macrophage-derived exosomal miRNAs can modulate in vivo and in vitro insulin sensitivity. Cell,2017,171(2): 372–384.e12. doi: 10.1016/j.cell. 2017.08.035.

LONG H, SUN B, CHENG L, et al. miR-139-5p Represses BMSC osteogenesis via targeting Wnt/β-catenin signaling pathway. DNA Cell Biol,2017,36(8): 715–724. doi: 10.1089/dna.2017.3657.

JIN Y, HONG F, BAO Q, et al. MicroRNA-145 suppresses osteogenic differentiation of human jaw bone marrow mesenchymal stem cells partially via targeting semaphorin 3A. Connect Tissue Res,2020,61(6): 577–585. doi: 10.1080/03008207.2019.1643334.

LIU X, ZHU W, WANG L, et al. miR-145-5p suppresses osteogenic differentiation of adipose-derived stem cells by targeting semaphorin 3A. In Vitro Cell Dev Biol Anim,2019,55(3): 189–202. doi: 10.1007/s11626-019-00318-7.

LI H, YUE L, XU H, et al. Curcumin suppresses osteogenesis by inducing miR-126a-3p and subsequently suppressing the WNT/LRP6 pathway. Aging (Albany NY),2019,11(17): 6983–6998. doi: 10.18632/aging.102232.

YANG C, LIU X, ZHAO K, et al. miRNA-21 promotes osteogenesis via the PTEN/PI3K/Akt/HIF-1α pathway and enhances bone regeneration in critical size defects. Stem Cell Res Ther,2019,10(1): 65. doi: 10.1186/s13287-019-1168-2.


Refbacks

  • There are currently no refbacks.