GATA4 regulates osteogenic differentiation by targeting miR‑144‑3p

Qiu,Tao; Li,Haotian; Lu,Tao; Shu,Liping; Chen,Chao; Wang,Chunqing

doi:10.3892/etm.2021.11006

GATA4 regulates osteogenic differentiation by targeting miR‑144‑3p

Authors:
- Tao Qiu
- Haotian Li
- Tao Lu
- Liping Shu
- Chao Chen
- Chunqing Wang
View Affiliations

Affiliations: Department of Orthopedic Trauma, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China, Center for Tissue Engineering and Stem Cell Research, Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China
Published online on: November 25, 2021 https://doi.org/10.3892/etm.2021.11006
Article Number: 83

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Numerous studies have demonstrated that microRNAs (miRNAs or miRs) play an important role in regulating osteogenic differentiation, but their specific regulatory mechanism requires further investigation. In the present study, it was revealed that during osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs), the expression level of miR‑144‑3p was decreased with increased osteogenic induction duration and was negatively associated with osteogenic marker gene expression. Overexpression of miR‑144‑3p inhibited osteogenic differentiation, while inhibition of miR‑144‑3p expression promoted osteogenic differentiation. In addition, dual‑luciferase activity analysis and adenovirus infection experiments revealed that GATA binding protein 4 targeted miR‑144‑3p for regulation and that overexpression of GATA4 promoted the expression of miR‑144‑3p. These data indicated that miR‑144‑3p plays a role in inhibiting BMSC osteogenic differentiation and that GATA4 inhibits osteogenic differentiation by targeting miR‑144‑3p expression.

View Figures

View References

1	Hendrickx G, Boudin E and Van Hul W: A look behind the scenes: The risk and pathogenesis of primary osteoporosis. Nat Rev Rheumatol. 11:462–474. 2015.PubMed/NCBI View Article : Google Scholar
2	Pouresmaeili F, Kamalidehghan B, Kamarehei M and Goh YM: A comprehensive overview on osteoporosis and its risk factors. Ther Clin Risk Manag. 14:2029–2049. 2018.PubMed/NCBI View Article : Google Scholar
3	Paspaliaris V and Kolios G: Stem cells in osteoporosis: From biology to new therapeutic approaches. Stem Cells Int. 2019(1730978)2019.PubMed/NCBI View Article : Google Scholar
4	Liu J, Wu M, Feng G, Li R, Wang Y and Jiao J: Downregulation of LINC00707 promotes osteogenic differentiation of human bone marrow-derived mesenchymal stem cells by regulating DKK1 via targeting miR-103a-3p. Int J Mol Med. 46:1029–1038. 2020.PubMed/NCBI View Article : Google Scholar
5	Shenoy A and Blelloch RH: Regulation of microRNA function in somatic stem cell proliferation and differentiation. Nat Rev Mol Cell Biol. 15:565–576. 2014.PubMed/NCBI View Article : Google Scholar
6	van Wijnen AJ, van de Peppel J, van Leeuwen JP, Lian JB, Stein GS, Westendorf JJ, Oursler MJ, Im HJ, Taipaleenmäki H, Hesse E, et al: MicroRNA functions in osteogenesis and dysfunctions in osteoporosis. Curr Osteoporos Rep. 11:72–82. 2013.PubMed/NCBI View Article : Google Scholar
7	Nugent M: MicroRNA function and dysregulation in bone tumors: The evidence to date. Cancer Manag Res. 6:15–25. 2014.PubMed/NCBI View Article : Google Scholar
8	Clark EA, Kalomoiris S, Nolta JA and Fierro FA: Concise review: MicroRNA function in multipotent mesenchymal stromal cells. Stem Cells. 32:1074–1082. 2014.PubMed/NCBI View Article : Google Scholar
9	Chen H, Ji X, She F, Gao Y and Tang P: miR-628-3p regulates osteoblast differentiation by targeting RUNX2: Possible role in atrophic non-union. Int J Mol Med. 39:279–286. 2017.PubMed/NCBI View Article : Google Scholar
10	Cui X, Wang S, Cai H, Lin Y, Zheng X, Zhang B and Xia C: Overexpression of microRNA-634 suppresses survival and matrix synthesis of human osteoarthritis chondrocytes by targeting PIK3R1. Sci Rep. 6(23117)2016.PubMed/NCBI View Article : Google Scholar
11	Chen J, Li K, Pang Q, Yang C, Zhang H, Wu F, Cao H, Liu H, Wan Y, Xia W, et al: Identification of suitable reference gene and biomarkers of serum miRNAs for osteoporosis. Sci Rep. 6(36347)2016.PubMed/NCBI View Article : Google Scholar
12	Panach L, Mifsut D, Tarín JJ, Cano A and García-Pérez M: Serum circulating microRNAs as biomarkers of osteoporotic fracture. Calcif Tissue Int. 97:495–505. 2015.PubMed/NCBI View Article : Google Scholar
13	Wang C, He H, Wang L, Jiang Y and Xu Y: Reduced miR-144-3p expression in serum and bone mediates osteoporosis pathogenesis by targeting RANK. Biochem Cell Biol. 96:627–635. 2018.PubMed/NCBI View Article : Google Scholar
14	Laforest B and Nemer M: GATA5 interacts with GATA4 and GATA6 in outflow tract development. Dev Biol. 358:368–378. 2011.PubMed/NCBI View Article : Google Scholar
15	Zhou P, He A and Pu WT: Regulation of GATA4 transcriptional activity in cardiovascular development and disease. Curr Top Dev Biol. 100:143–169. 2012.PubMed/NCBI View Article : Google Scholar
16	Li Q, Shen P, Zeng S and Liu P: TIEG1 inhibits angiotensin II-induced cardiomyocyte hypertrophy by inhibiting transcription factor GATA4. J Cardiovasc Pharmacol. 66:196–203. 2015.PubMed/NCBI View Article : Google Scholar
17	Song I, Kim K, Kim JH, Lee YK, Jung HJ, Byun HO, Yoon G and Kim N: GATA4 negatively regulates osteoblast differentiation by downregulation of Runx2. BMB Rep. 47:463–468. 2014.PubMed/NCBI View Article : Google Scholar
18	Snykers S, Vanhaecke T and Rogiers V: Isolation of rat bone marrow stem cells. Methods Mol Biol. 320:265–372. 2006.PubMed/NCBI View Article : Google Scholar
19	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar
20	Huang C, Geng J, Wei X, Zhang R and Jiang S: miR-144-3p regulates osteogenic differentiation and proliferation of murine mesenchymal stem cells by specifically targeting Smad4. FEBS Lett. 590:795–807. 2016.PubMed/NCBI View Article : Google Scholar
21	Yuan Y, Zhang L, Tong X, Zhang M, Zhao Y, Guo J, Lei L, Chen X, Tickner J, Xu J, et al: Mechanical stress regulates bone metabolism through microRNAs. J Cell Physiology. 232:1239–1245. 2017.PubMed/NCBI View Article : Google Scholar
22	Xie Y, Zhang L, Gao Y, Ge W and Tang P: The multiple roles of microrna-223 in regulating bone metabolism. Molecules. 20:19433–19448. 2015.PubMed/NCBI View Article : Google Scholar
23	Sugimachi K, Matsumura T, Hirata H, Uchi R, Ueda M, Ueo H, Shinden Y, Iguchi T, Eguchi H, Shirabe K, et al: Identification of a bona fide microRNA biomarker in serum exosomes that predicts hepatocellular carcinoma recurrence after liver transplantation. Br J Cancer. 112:532–538. 2015.PubMed/NCBI View Article : Google Scholar
24	Witwer KW: Circulating microRNA biomarker studies: Pitfalls and potential solutions. Clin Chem. 61:56–63. 2015.PubMed/NCBI View Article : Google Scholar
25	Wang X, Guo B, Li Q, Peng J, Yang Z, Wang A, Li D, Hou Z, Lv K, Kan G, et al: miR-214 targets ATF4 to inhibit bone formation. Nat Med. 19:93–100. 2013.PubMed/NCBI View Article : Google Scholar
26	Matsumura T, Sugimachi K, Iinuma H, Takahashi Y, Kurashige J, Sawada G, Ueda M, Uchi R, Ueo H, Takano Y, et al: Exosomal microRNA in serum is a novel biomarker of recurrence in human colorectal cancer. Br J Cancer. 113:275–281. 2015.PubMed/NCBI View Article : Google Scholar
27	Huang K, Fu J, Zhou W, Li W, Dong S, Yu S, Hu Z, Wang H and Xie Z: MicroRNA-125b regulates osteogenic differentiation of mesenchymal stem cells by targeting Cbfβ in vitro. Biochimie. 102:47–55. 2014.PubMed/NCBI View Article : Google Scholar
28	Li Z, Zhang W and Huang Y: miRNA-133a is involved in the regulation of postmenopausal osteoporosis through promoting osteoclast differentiation. Acta Biochim Biophys Sin (Shanghai). 50:273–280. 2018.PubMed/NCBI View Article : Google Scholar
29	Chen T, Che X, Han P, Lu J, Wang C, Liang B, Hou Z, Wei X, Wei L and Li P: MicroRNA-1 promotes cartilage matrix synthesis and regulates chondrocyte differentiation via post-transcriptional suppression of Ihh expression. Mol Med Rep. 22:2404–2414. 2020.PubMed/NCBI View Article : Google Scholar
30	Zhong L, Chiusa M, Cadar AG, Lin A, Samaras S, Davidson JM and Lim CC: Targeted inhibition of ANKRD1 disrupts sarcomeric ERK-GATA4 signal transduction and abrogates phenylephrine-induced cardiomyocyte hypertrophy. Cardiovasc Res. 106:261–271. 2015.PubMed/NCBI View Article : Google Scholar
31	Song I, Jeong BC, Choi YJ, Chung YS and Kim N: GATA4 negatively regulates bone sialoprotein expression in osteoblasts. BMB Rep. 49:343–348. 2016.PubMed/NCBI View Article : Google Scholar
32	Khalid AB, Slayden AV, Kumpati J, Perry CD, Berryhill SB, Crawford JA, Fatima I, Morselli M, Pellegrini M, Miranda-Carboni GA and Krum SA: GATA4 represses RANKL in osteoblasts via multiple long-range enhancers to regulate osteoclast differentiation. Bone. 116:78–86. 2018.PubMed/NCBI View Article : Google Scholar
33	Khalid AB, Slayden AV, Kumpati J, Perry CD, Osuna MAL, Arroyo SR, Miranda-Carboni GA and Krum SA: GATA4 directly regulates runx2 expression and osteoblast differentiation. JBMR Plus. 2:81–91. 2018.PubMed/NCBI View Article : Google Scholar
34	Miranda-Carboni GA, Guemes M, Bailey S, Anaya E, Corselli M, Peault B and Krum SA: GATA4 regulates estrogen receptor-alpha-mediated osteoblast transcription. Mol Endocrino. 25:1126–1136. 2011.PubMed/NCBI View Article : Google Scholar
35	Güemes M, Garcia AJ, Rigueur D, Runke S, Wang W, Zhao G, Mayorga VH, Atti E, Tetradis S, Péault B, et al: GATA4 is essential for bone mineralization via ERα and TGFβ/BMP pathways. J Bone Miner Res. 29:2676–2687. 2014.PubMed/NCBI View Article : Google Scholar
36	Guo S, Zhang Y, Zhou T, Wang D, Weng Y, Wang L and Ma J: Role of GATA binding protein 4 (GATA4) in the regulation of tooth development via GNAI3. Sci Rep. 7(1534)2017.PubMed/NCBI View Article : Google Scholar
37	Zhang X, Wang X, Zhu H, Zhu C, Wang Y, Pu WT, Jegga AG and Fan GC: Synergistic effects of the GATA-4-mediated miR-144/451 cluster in protection against simulated ischemia/reperfusion-induced cardiomyocyte death. J Mol Cell Cardiol. 49:841–850. 2010.PubMed/NCBI View Article : Google Scholar
38	Kureel J, Dixit M, Tyagi AM, Mansoori MN, Srivastava K, Raghuvanshi A, Maurya R, Trivedi R, Goel A and Singh D: miR-542-3p suppresses osteoblast cell proliferation and differentiation, targets BMP-7 signaling and inhibits bone formation. Cell Death Dis. 5(e1050)2014.PubMed/NCBI View Article : Google Scholar