MicroRNA‑186‑5p Mediates Osteoblastic Differentiation and Cell Viability by Targeting CXCL13 in Non‑traumatic Osteonecrosis

Overview

Journal Mol Med Rep

Specialty Molecular Biology

Date 2019 Nov 9

PMID 31702033

Citations 9

Authors

Weihua Xu

Jin Li

Hongtao Tian

Ruoyu Wang

Yong Feng

Jing Tang

Jie Jia

Affiliations

Soon will be listed here.

Abstract

MicroRNAs (miRs) serve varying and important roles in the pathogenesis of non‑traumatic osteonecrosis (ON). However, the role miR‑186‑5p serves in the pathogenesis of osteonecrosis remains unknown and the clinical outcome of ON is still uncertain. The aim of the present study was to determine the expression characteristics, biological function and molecular mechanisms of miR‑186‑5p, which is associated with cancer development and progression, in osteoblastic differentiation and cell viability. The results of the present study showed that the expression levels of miR‑186‑5p were significantly higher in clinical non‑traumatic ON compared with osteoarthritis samples (P=0.0001). An inverse association was observed between miR‑186‑5p and CXCL13 expression levels. Furthermore, miR‑186‑5p inhibited phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signaling, downregulated osteoblast‑specific markers and reduced the viability and differentiation of human mesenchymal stem cells from bone marrow (HMSC‑bm) through targeting CXCL13. Increasing expression of CXCL13 in HMSC‑bm cells partially restored miR‑186‑5p‑mediated inhibition. In conclusion, abrogation of PI3K/AKT signaling triggered by miR‑186‑5p/CXCL13 may contribute to ON pathogenesis. These results highlight the possible clinical value of miR‑186‑5p in treatment for non‑traumatic ON.

Citing Articles

Hollow Hydroxyapatite Microspheres Loaded with rhCXCL13 to Recruit BMSC for Osteogenesis and Synergetic Angiogenesis to Promote Bone Regeneration in Bone Defects.

Zeng J, Xiong S, Zhou J, Wei P, Guo K, Wang F Int J Nanomedicine. 2023; 18:3509-3534.

PMID: 37404852 PMC: 10317543. DOI: 10.2147/IJN.S408905.

Recent advancements of miRNAs in the treatment of bone diseases and their delivery potential.

Sharma A, Lee Y, Lee S Curr Res Pharmacol Drug Discov. 2023; 4:100150.

PMID: 36691422 PMC: 9860349. DOI: 10.1016/j.crphar.2022.100150.

Effect of condylar chondrocyte exosomes on condylar cartilage osteogenesis in rats under tensile stress.

Shi Y, Shao J, Zhang Z, Zhang J, Lu H Front Bioeng Biotechnol. 2022; 10:1061855.

PMID: 36561044 PMC: 9766957. DOI: 10.3389/fbioe.2022.1061855.

Bioinformatic analysis of the RNA expression patterns in microgravity-induced bone loss.

Zhang X, Xue T, Hu Z, Guo X, Li G, Wang Y Front Genet. 2022; 13:985025.

PMID: 36425065 PMC: 9681495. DOI: 10.3389/fgene.2022.985025.

The Emerging Role of MicroRNAs in Bone Diseases and Their Therapeutic Potential.

Bravo Vazquez L, Moreno Becerril M, Mora Hernandez E, Leon Carmona G, Aguirre Padilla M, Chakraborty S Molecules. 2022; 27(1).

PMID: 35011442 PMC: 8746945. DOI: 10.3390/molecules27010211.

References

Yamasaki K, Nakasa T, Miyaki S, Yamasaki T, Yasunaga Y, Ochi M . Angiogenic microRNA-210 is present in cells surrounding osteonecrosis. J Orthop Res. 2012; 30(8):1263-70. DOI: 10.1002/jor.22079. View

Feng Y, Yang S, Xiao B, Xu W, Ye S, Xia T . Decreased in the number and function of circulation endothelial progenitor cells in patients with avascular necrosis of the femoral head. Bone. 2009; 46(1):32-40. DOI: 10.1016/j.bone.2009.09.001. View

Tian F, Ji X, Xiao W, Wang B, Wang F . CXCL13 Promotes Osteogenic Differentiation of Mesenchymal Stem Cells by Inhibiting miR-23a Expression. Stem Cells Int. 2015; 2015:632305. PMC: 4345275. DOI: 10.1155/2015/632305. View

Trapnell C, Williams B, Pertea G, Mortazavi A, Kwan G, van Baren M . Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat Biotechnol. 2010; 28(5):511-5. PMC: 3146043. DOI: 10.1038/nbt.1621. View

Kim S, Lee Y, Bae Y . MiR-186, miR-216b, miR-337-3p, and miR-760 cooperatively induce cellular senescence by targeting α subunit of protein kinase CKII in human colorectal cancer cells. Biochem Biophys Res Commun. 2012; 429(3-4):173-9. DOI: 10.1016/j.bbrc.2012.10.117. View

Lu K, Zeng D, Zhang Y, Xia L, Xu L, Kaplan D . BMP-2 gene modified canine bMSCs promote ectopic bone formation mediated by a nonviral PEI derivative. Ann Biomed Eng. 2011; 39(6):1829-39. PMC: 3406185. DOI: 10.1007/s10439-011-0276-7. View

Zhu Z, Zhang X, Guo H, Fu L, Pan G, Sun Y . CXCL13-CXCR5 axis promotes the growth and invasion of colon cancer cells via PI3K/AKT pathway. Mol Cell Biochem. 2014; 400(1-2):287-95. DOI: 10.1007/s11010-014-2285-y. View

Nishimori S, Tanaka Y, Chiba T, Fujii M, Imamura T, Miyazono K . Smad-mediated transcription is required for transforming growth factor-beta 1-induced p57(Kip2) proteolysis in osteoblastic cells. J Biol Chem. 2001; 276(14):10700-5. DOI: 10.1074/jbc.M007499200. View

Yuan C, Cai J . Time-series expression profile analysis of fracture healing in young and old mice. Mol Med Rep. 2017; 16(4):4529-4536. PMC: 5647013. DOI: 10.3892/mmr.2017.7198. View

10.

Li Z, Liao W, Zhao Q, Liu M, Xia W, Yang Y . Angiogenesis and bone regeneration by allogeneic mesenchymal stem cell intravenous transplantation in rabbit model of avascular necrotic femoral head. J Surg Res. 2013; 183(1):193-203. DOI: 10.1016/j.jss.2012.11.031. View

11.

Guo H, Ingolia N, Weissman J, Bartel D . Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature. 2010; 466(7308):835-40. PMC: 2990499. DOI: 10.1038/nature09267. View

12.

Adapala N, Kim H . Comprehensive Genome-Wide Transcriptomic Analysis of Immature Articular Cartilage following Ischemic Osteonecrosis of the Femoral Head in Piglets. PLoS One. 2016; 11(4):e0153174. PMC: 4821627. DOI: 10.1371/journal.pone.0153174. View

13.

Cristino S, Piacentini A, Manferdini C, Codeluppi K, Grassi F, Facchini A . Expression of CXC chemokines and their receptors is modulated during chondrogenic differentiation of human mesenchymal stem cells grown in three-dimensional scaffold: evidence in native cartilage. Tissue Eng Part A. 2008; 14(1):97-105. DOI: 10.1089/ten.a.2007.0121. View

14.

van Wijnen A, van de Peppel J, van Leeuwen J, Lian J, Stein G, Westendorf J . MicroRNA functions in osteogenesis and dysfunctions in osteoporosis. Curr Osteoporos Rep. 2013; 11(2):72-82. PMC: 3678273. DOI: 10.1007/s11914-013-0143-6. View

15.

Cai J, Wu J, Zhang H, Fang L, Huang Y, Yang Y . miR-186 downregulation correlates with poor survival in lung adenocarcinoma, where it interferes with cell-cycle regulation. Cancer Res. 2012; 73(2):756-66. DOI: 10.1158/0008-5472.CAN-12-2651. View

16.

Rauhut R, Lendeckel W, Tuschl T . Identification of novel genes coding for small expressed RNAs. Science. 2001; 294(5543):853-8. DOI: 10.1126/science.1064921. View

17.

Tan G, Kang P, Pei F . Glucocorticoids affect the metabolism of bone marrow stromal cells and lead to osteonecrosis of the femoral head: a review. Chin Med J (Engl). 2012; 125(1):134-9. View

18.

Gangji V, De Maertelaer V, Hauzeur J . Autologous bone marrow cell implantation in the treatment of non-traumatic osteonecrosis of the femoral head: Five year follow-up of a prospective controlled study. Bone. 2011; 49(5):1005-9. DOI: 10.1016/j.bone.2011.07.032. View

19.

Ruegg C, Hasmim M, Lejeune F, Alghisi G . Antiangiogenic peptides and proteins: from experimental tools to clinical drugs. Biochim Biophys Acta. 2005; 1765(2):155-77. DOI: 10.1016/j.bbcan.2005.09.003. View

20.

Hutchins A, Jauch R, Dyla M, Miranda-Saavedra D . glbase: a framework for combining, analyzing and displaying heterogeneous genomic and high-throughput sequencing data. Cell Regen. 2014; 3(1):1. PMC: 4230833. DOI: 10.1186/2045-9769-3-1. View