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Current Stem Cell Research & Therapy

Editor-in-Chief

ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Research Article

LRRC75A-AS1 Inhibits Chondrogenic Differentiation of Bmscs via Targeting the Mir-140-3p/Wnt/Β-Catenin Pathway

Author(s): Pengfei Shen, Bin Wang, Chong Zheng, Jie Pei, Daofu Gan and Zikang Xie*

Volume 18, Issue 8, 2023

Published on: 14 February, 2023

Page: [1142 - 1149] Pages: 8

DOI: 10.2174/1574888X18666230116141524

Price: $65

Abstract

Background: Bone marrow mesenchymal stem cells (BMSCs) are pluripotent cells with the ability to differentiate into adipocytes, chondrocytes, and osteoblasts. BMSCs are widely used in regenerative medicine and cartilage tissue engineering. Role of lncRNA LRRC75A-AS1 (leucine-rich repeat containing 75A antisense RNA 1) in the chondrogenic differentiation of BMSCs was investigated in this study.

Methods: BMSCs were isolated from rat bone marrow and then identified using flow cytometry. Alcian blue staining was used to detect chondrogenic differentiation. The effect of LRRC75A-AS1 on chondrogenic differentiation was assessed by western blot. The downstream target of LRRC75A-AS1 was determined by dual luciferase activity assay.

Results: BMSCs were identified with positive CD29 and CD44 staining and negative staining of CD34 and CD45. LRRC75A-AS1 was decreased during the chondrogenic differentiation of BMSCs. Silencing of LRRC75A-AS1 increased collagen II (COL II), aggrecan and SOX9 and promoted chondrogenic differentiation. However, over-expression of LRRC75A-AS1 inhibited chondrogenic differentiation. miR- 140-3p was increased during chondrogenic differentiation and interacted with LRRC75A-AS1. miR-140- 3p bind to wnt3a, and inhibition of miR-140-3p up-regulated wnt3a and nuclear β- catenin expression. Wnt3a and nuclear β-catenin were decreased during chondrogenic differentiation. Inhibition of miR-140- 3p attenuated LRRC75A-AS1 deficiency-induced up-regulation of COL II, aggrecan and SOX9.

Conclusion: LRRC75A-AS1 suppressed chondrogenic differentiation of BMSCs through down-regulation of miR-140-3p and up-regulation of the wnt/β-catenin pathway.

Graphical Abstract

[1]
Kurz B, Lemke AK, Fay J, Pufe T, Grodzinsky AJ, Schünke M. Pathomechanisms of cartilage destruction by mechanical injury. Ann Anat 2005; 187(5-6): 473-85.
[http://dx.doi.org/10.1016/j.aanat.2005.07.003] [PMID: 16320827]
[2]
Deng P, Liang H, Xie K, et al. Study on the molecular mechanism of Guizhi Jia Shaoyao decoction for the treatment of knee osteoarthritis by utilizing network pharmacology and molecular docking technology. Allergol Immunopathol 2021; 49(6): 16-30.
[http://dx.doi.org/10.15586/aei.v49i6.484] [PMID: 34761652]
[3]
Coaccioli S. Recommendations for osteoarthritis. Signa Vitae 2021; 17(S1): 60-0.
[http://dx.doi.org/10.22514/sv.2021.203]
[4]
Jhan SW, Wang CJ, Wu KT, et al. Comparison of extracorporeal shockwave therapy with non-steroid anti-inflammatory drugs and intra-articular hyaluronic acid injection for early osteoarthritis of the knees. Biomedicines 2022; 10(2): 202.
[http://dx.doi.org/10.3390/biomedicines10020202] [PMID: 35203417]
[5]
Robey PG. “Mesenchymal stem cells”: fact or fiction, and implications in their therapeutic use. F1000 Res 2017; 6: 524.
[http://dx.doi.org/10.12688/f1000research.10955.1] [PMID: 28491279]
[6]
Hardingham T, Tew S, Murdoch A. Tissue engineering: Chondrocytes and cartilage. Arthritis Res 2002; 4 (Suppl. 3): S63-8.
[http://dx.doi.org/10.1186/ar561] [PMID: 12110124]
[7]
Hu N, Gao Y, Jayasuriya CT, et al. Chondrogenic induction of human osteoarthritic cartilage-derived mesenchymal stem cells activates mineralization and hypertrophic and osteogenic gene expression through a mechanomiR. Arthritis Res Ther 2019; 21(1): 167.
[http://dx.doi.org/10.1186/s13075-019-1949-0] [PMID: 31287025]
[8]
He CP, Jiang XC, Chen C, et al. The function of lncRNAs in the pathogenesis of osteoarthritis. Bone Joint Res 2021; 10(2): 122-33.
[http://dx.doi.org/10.1302/2046-3758.102.BJR-2020-0228.R1] [PMID: 33560158]
[9]
Wang J, Liu S, Shi J, et al. The role of lncRNAs in osteogenic differentiation of bone marrow mesenchymal stem cells. Curr Stem Cell Res Ther 2020; 15(3): 243-9.
[http://dx.doi.org/10.2174/1574888X15666191227113742] [PMID: 31880266]
[10]
Yu X, Song MS, Rong PZ, et al. LncRNA SNHG1 modulates adipogenic differentiation of BMSCs by promoting DNMT1 mediated Opg hypermethylation via interacting with PTBP1. J Cell Mol Med 2022; 26(1): 60-74.
[http://dx.doi.org/10.1111/jcmm.16982] [PMID: 34854215]
[11]
Shan W. The association between lncRNA LRRC75A-AS1 and the clinical characteristics in neuroblastoma. Biomed J Sci Technol Res 2020; p. 28.
[12]
Li S, Wu D, Jia H, Zhang Z. Long non-coding RNA LRRC75A-AS1 facilitates triple negative breast cancer cell proliferation and invasion via functioning as a ceRNA to modulate BAALC. Cell Death Dis 2020; 11(8): 643.
[http://dx.doi.org/10.1038/s41419-020-02821-2] [PMID: 32811810]
[13]
Chen J, Lan J, Ye Z, et al. Long noncoding RNA LRRC75A-AS1 inhibits cell proliferation and migration in colorectal carcinoma. Exp Biol Med (Maywood) 2019; 244(14): 1137-43.
[http://dx.doi.org/10.1177/1535370219874339] [PMID: 31505952]
[14]
Shi C, Zheng W, Wang J. lncRNA-CRNDE regulates BMSC chondrogenic differentiation and promotes cartilage repair in osteoarthritis through SIRT1/SOX9. Mol Cell Biochem 2021; 476(4): 1881-90.
[http://dx.doi.org/10.1007/s11010-020-04047-4] [PMID: 33479807]
[15]
Ng LJ, Wheatley S, Muscat GEO, et al. SOX9 binds DNA, activates transcription, and coexpresses with type II collagen during chondrogenesis in the mouse. Dev Biol 1997; 183(1): 108-21.
[http://dx.doi.org/10.1006/dbio.1996.8487] [PMID: 9119111]
[16]
Zheng J, Lin Y, Tang F, et al. Promotive role of CircATRNL1 on chondrogenic differentiation of BMSCs mediated by miR-338-3p. Arch Med Res 2021; 52(5): 514-22.
[http://dx.doi.org/10.1016/j.arcmed.2021.02.003] [PMID: 33610389]
[17]
Xu S, Wu X. miR-134 inhibits chondrogenic differentiation of bone marrow mesenchymal stem cells by targetting SMAD6. Biosci Rep 2019; 39(1): BSR20180921.
[http://dx.doi.org/10.1042/BSR20180921] [PMID: 30135141]
[18]
Liu J, Yao Y, Huang J, et al. Comprehensive analysis of lncRNA-miRNA-mRNA networks during osteogenic differentiation of bone marrow mesenchymal stem cells. BMC Genomics 2022; 23(1): 425.
[http://dx.doi.org/10.1186/s12864-022-08646-x] [PMID: 35672672]
[19]
Kenyon JD, Sergeeva O, Somoza RA, et al. Analysis of -5p and -3p strands of miR-145 and miR-140 during mesenchymal stem cell chondrogenic differentiation. Tissue Eng Part A 2019; 25(1-2): 80-90.
[http://dx.doi.org/10.1089/ten.tea.2017.0440] [PMID: 29676203]
[20]
Karlsen T, Jakobsen R, Mikkelsen T, Brinchmann J. microRNA-140 targets RALA and regulates chondrogenic differentiation of human mesenchymal stem cells by translational enhancement of SOX9 and ACAN. Stem Cells Dev 2013; 23(3): 290-304.
[21]
Zhong H, Hao L, Li X, Wang C, Wu X. Anti-inflammatory role of trilobatin on lipopolysaccharide-induced acute lung injury through activation of AMPK/GSK3β-Nrf2 pathway. Signa Vitae 2020; 16(2): 160-6.
[22]
Zhang Y, Huang X, Yuan Y. MicroRNA-410 promotes chondrogenic differentiation of human bone marrow mesenchymal stem cells through down-regulating Wnt3a. Am J Transl Res 2017; 9(1): 136-45.
[PMID: 28123640]
[23]
Han L, Li Z, Jiang Y, Jiang Z, Tang L. SNHG29 regulates miR-223-3p/CTNND1 axis to promote glioblastoma progression via Wnt/β-catenin signaling pathway. Cancer Cell Int 2019; 19(1): 345.
[http://dx.doi.org/10.1186/s12935-019-1057-x] [PMID: 31889897]
[24]
Wu S, Wang H, Pan Y, Yang X, Wu D. miR-140-3p enhances cisplatin sensitivity and attenuates stem cell-like properties through repressing Wnt/β-catenin signaling in lung adenocarcinoma cells. Exp Ther Med 2020; 20(2): 1664-74.
[http://dx.doi.org/10.3892/etm.2020.8847] [PMID: 32765679]

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