MicroRNAs Involved in the Regulation of Angiogenesis in Bone Regeneration
- 126 Downloads
MicroRNAs (miRNAs) as a newly founded and thriving non-coding endogenous class of molecules which regulate many cellular pathways after transcription have been extensively investigated in regenerative medicine. In this systematic review, we sought to analyze miRNAs-mediated therapeutic approaches for influencing angiogenesis in bone tissue/bone regeneration. An electronic search in MEDLINE, Scopus, EMBASE, Cochrane library, web of science, and google scholar with no time limit were done on English publications. All types of original articles which a miRNA for angiogenesis in bone regeneration were included in our review. In the process of reviewing, we used PRISMA guideline and, SYRCLE’s and science in risk assessment and policy tools for analyzing risk of bias. Among 751 initial retrieved records, 16 studies met the inclusion criteria and were fully assessed in this review. 275 miRNAs, one miRNA 195~497 cluster, and one Cysteine-rich 61 short hairpin RNA were differentially expressed during bone regeneration with 24 predicted targets reported in these studies. Among these miRNAs, miRNA-7b, -9, -21, -26a, -27a, -210, -378, -195~497 cluster, -378 and -675 positively promoted both angiogenesis and osteogenesis, whereas miRNA-10a, -222 and -494 inhibited both processes. The most common target was vasculoendothelial growth factor-signaling pathway. Recent evidence has demonstrated that miRNAs actively participated in angio-osteogenic coupling that can improve their therapeutic potentials for the treatment of bone-related diseases and bone regeneration. However, there is still need for further research to unravel the exact mechanisms.
KeywordsMicroRNA AngiomiR Angiogenesis Bone angiogenesis Bone regeneration Bone tissue engineering
AMP-activated protein kinase
Dendritic cell-specific transmembrane protein
F-box WD-40 domain protein
Notch intercellular cytoplasmic domain
Prolyl 4-hydroxylase possessing a transmembrane domain
Protein kinase C-α
Runt-related transcription factor 2
Secreted frizzled-related protein 1
Transforming growth factor-activated kinase 1
Vasculoendothelial growth factor
This project in part is funded by The University of Queensland International (UQI) Scholarship.
SH and QY initiated this study. SH, QS and HY designed the review methodology. SH and AN prepared the initial draft of the study and made revisions. QY and YH critically reviewed included articles, and proofread the final draft of the manuscript.
Compliance with Ethical Standards
Conflict of interest
The authors have no conflicts of interest related to this study.
Research Involving Human and Animal Participants
Due to the essence of this study, as a review article, there were not any human or animal participants, but we included the studies which all of them have ethical approval.
This is not applicable for this study.
- 11.Xia M (2008) Great potential of microRNA in cancer stem cell. Mol Cancer J 4:79–89Google Scholar
- 35.Zha X, Sun B, Zhang R, Li C, Yan Z, Chen J (2018) Regulatory effect of microRNA-34a on osteogenesis and angiogenesis in glucocorticoid-induced osteonecrosis of the femoral head. J Orthop Res 36:417–424Google Scholar
- 39.Yoshizuka M, Nakasa T, Kawanishi Y, Hachisuka S, Furuta T, Miyaki S, Adachi N, Ochi M (2016) Inhibition of microRNA-222 expression accelerates bone healing with enhancement of osteogenesis, chondrogenesis, and angiogenesis in a rat refractory fracture model. J Orthop Sci 21:852–858CrossRefGoogle Scholar
- 66.Yang M, Li CJ, Sun X, Guo Q, Xiao Y, Su T, Tu ML, Peng H, Lu Q, Liu Q, He HB, Jiang TJ, Lei MX, Wan M, Cao X, Luo XH (2017) MiR-497 approximately 195 cluster regulates angiogenesis during coupling with osteogenesis by maintaining endothelial Notch and HIF-1alpha activity. Nat Commun 8:16003CrossRefGoogle Scholar
- 71.You L, Gu W, Chen L, Pan L, Chen J, Peng Y (2014) MiR-378 overexpression attenuates high glucose-suppressed osteogenic differentiation through targeting CASP3 and activating PI3 K/Akt signaling pathway. Int J Clin Exp Pathol 7:7249–7261Google Scholar
- 73.Costa V, Raimondi L, Conigliaro A, Salamanna F, Carina V, De Luca A, Bellavia D, Alessandro R, Fini M, Giavaresi G (2017) Hypoxia-inducible factor 1Alpha may regulate the commitment of mesenchymal stromal cells toward angio-osteogenesis by mirna-675-5P. Cytotherapy 19:1412–1425CrossRefGoogle Scholar
- 74.Aguado-Fraile E, Ramos E, Conde E, Rodríguez M, Liaño F, García-Bermejo ML (2013) MicroRNAs in the kidney: novel biomarkers of acute kidney injury. Nefrología (English Edition) 33:826–834Google Scholar
- 75.Tang H (2013) miR-10a regulates epithelial-mesenchymal transition and adhesion and angiogenesis in hepatoma. In: Federation of American Societies for Experimental Biology, p lb153-lb153Google Scholar
- 78.Yoshizuka M, Nakasa T, Kawanishi Y, Hachisuka S, Furuta T, Miyaki S, Adachi N, Ochi M (2016) Inhibition of microRNA-222 expression accelerates bone healing with enhancement of osteogenesis, chondrogenesis, and angiogenesis in a rat refractory fracture model. J Orthop Sci 21:852–858CrossRefGoogle Scholar
- 80.Welten SM, Bastiaansen AJ, de Jong RC, de Vries MR, Peters EA, Boonstra MC, Sheikh SP, La Monica N, Kandimalla ER, Quax PH, Nossent AY (2014) Inhibition of 14q32 MicroRNAs miR-329, miR-487b, miR-494, and miR-495 increases neovascularization and blood flow recovery after ischemia. Circ Res 115:696–708CrossRefGoogle Scholar
- 86.Lu X, Deng M, He H, Zeng D, Zhang W (2013) miR-125b regulates osteogenic differentiation of human bone marrow mesenchymal stem cells by targeting Smad4. J Cent South Univ Med Sci 38:341–346Google Scholar
- 87.Ventura A, Young AG, Winslow MM, Lintault L, Meissner A, Erkeland SJ, Newman J, Bronson RT, Crowley D, Stone JR, Jaenisch R, Sharp PA, Jacks T (2008) Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters. Cell 132:875–886CrossRefGoogle Scholar
- 89.Bonauer A, Carmona G, Iwasaki M, Mione M, Koyanagi M, Fischer A, Burchfield J, Fox H, Doebele C, Ohtani K, Chavakis E, Potente M, Tjwa M, Urbich C, Zeiher AM, Dimmeler S (2009) MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice. Science 324:1710–1713CrossRefGoogle Scholar