miR‑29b enhances the proliferation and migration of bone marrow mesenchymal stem cells in rats with castration‑induced osteoporosis through the PI3K/AKT and TGF‑β/Smad signaling pathways Retraction in /10.3892/etm.2022.11644

Wang,Yuhui; Han,Xiangmin; Zang,Tongxin; Kang,Ping; Jiang,Wei; Niu,Niu

doi:10.3892/etm.2020.9045

miR‑29b enhances the proliferation and migration of bone marrow mesenchymal stem cells in rats with castration‑induced osteoporosis through the PI3K/AKT and TGF‑β/Smad signaling pathways

Retraction in: /10.3892/etm.2022.11644

Authors:
- Yuhui Wang
- Xiangmin Han
- Tongxin Zang
- Ping Kang
- Wei Jiang
- Niu Niu
View Affiliations

Affiliations: Department of Clinical Laboratory, Affiliated Hospital of Beihua University, Jilin, Jilin 132011, P.R. China, Department of Clinical Laboratory, Jinan Zhangqiu District Hospital of TCM, Jinan, Shandong 250200, P.R. China, Department of Orthopaedics, Qingdao Central Hospital, Qingdao University, Qingdao, Shandong 266042, P.R. China, Department of Rehabilitation, The People's Hospital of Zhangqiu Area, Jinan, Shandong 250200, P.R. China, Department of Cardio‑Thoracic Surgery, The People's Hospital of Zhangqiu Area, Jinan, Shandong 250200, P.R. China, Department of Clinical Laboratory, Qingdao No. 9 People's Hospital, Qingdao, Shandong 266002, P.R. China
Published online on: July 24, 2020 https://doi.org/10.3892/etm.2020.9045
Pages: 3185-3195
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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

The aim of the present study was to investigate the role of microRNA (miR)-29b in the proliferation and migration of bone marrow mesenchymal stem cells (BMSCs) in rats with castration‑induced osteoporosis and the relevant mechanisms. The gene expression profiling microarray technique was utilized to sequence the BMSCs with overexpressed miR‑29b. The intersection of the potential targets and the genes downregulated in the sequencing were utilized for GO enrichment analysis. Gene set enrichment analysis (GSEA) was employed to analyze the effect of miR‑29b on signaling pathways. Additionally, the effects of miR‑29b overexpression on the phosphatidylinositol 3‑kinase (PI3K)/protein kinase B (AKT) and transforming growth factor‑β (TGF‑β)/Drosophila mothers against decapentaplegic protein (Smad) signaling pathways were detected via RT‑qPCR assay and western blotting. The expression level of miR‑29b was found to be significantly reduced in bone marrow tissues of postmenopausal osteoporosis patients and BMSCs of rats with castration‑induced osteoporosis established via ovariectomy. Based on transcriptome sequencing and bioinformatics software prediction, 76 potential targets of miR‑29b were obtained, which were distinctly enriched in such biological processes as cell proliferation, cell cycle, cell migration and cell adhesion. The results of CCK‑8 and EdU assays showed that overexpression of miR‑29b overtly promoted the proliferation of BMSCs in rats with castration‑induced osteoporosis. Moreover, the Transwell assay results revealed that the overexpression of miR‑29b significantly facilitated the migration of BMSCs in rats with castration‑induced osteoporosis. According to RT‑qPCR assay and western blotting, miR‑29b activated the PI3K/AKT and TGF‑β/Smad signaling pathways. miR‑29b exhibited a clearly lower expression level in the bone marrow tissues of the postmenopausal osteoporosis patients and BMSCs of rats with castration‑induced osteoporosis established via ovariectomy. Overexpression of miR‑29b was able to enhance the proliferation and migration ability of BMSCs in rats with castration‑induced osteoporosis, and such an enhancement may be correlated with the activation of the PI3K/AKT and TGF‑β/Smad signaling pathways.

View Figures

View References

1	Black DM and Rosen CJ: Postmenopausal osteoporosis. N Engl J Med. 374:2096–2097. 2016.PubMed/NCBI View Article : Google Scholar
2	Qiao L, Liu D, Li CG and Wang YJ: MiR-203 is essential for the shift from osteogenic differentiation to adipogenic differentiation of mesenchymal stem cells in postmenopausal osteoporosis. Eur Rev Med Pharmacol Sci. 22:5804–5814. 2018.PubMed/NCBI View Article : Google Scholar
3	Jing H, Liao L, Su X, Shuai Y, Zhang X, Deng Z and Jin Y: Declining histone acetyltransferase GCN5 represses BMSC-mediated angiogenesis during osteoporosis. FASEB J. 31:4422–4433. 2017.PubMed/NCBI View Article : Google Scholar
4	Paraskevopoulou MD and Hatzigeorgiou AG: Analyzing miRNA-lncRNA interactions. Methods Mol Biol. 1402:271–286. 2016.PubMed/NCBI View Article : Google Scholar
5	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
6	Letarouilly JG, Broux O and Clabaut A: New insights into the epigenetics of osteoporosis. Genomics. 111:793–798. 2019.PubMed/NCBI View Article : Google Scholar
7	Seeliger C, Karpinski K, Haug AT, Vester H, Schmitt A, Bauer JS and van Griensven M: Five freely circulating miRNAs and bone tissue miRNAs are associated with osteoporotic fractures. J Bone Miner Res. 29:1718–1728. 2014.PubMed/NCBI View Article : Google Scholar
8	Bedene A, Mencej Bedrač S, Ješe L, Marc J, Vrtačnik P, Preželj J, Kocjan T, Kranjc T and Ostanek B: MiR-148a the epigenetic regulator of bone homeostasis is increased in plasma of osteoporotic postmenopausal women. Wien Klin Wochenschr. 128 (Suppl 7):S519–S526. 2016.PubMed/NCBI View Article : Google Scholar
9	Guo DW, Han YX, Cong L, Liang D and Tu GJ: Resveratrol prevents osteoporosis in ovariectomized rats by regulating microRNA-338-3p. Mol Med Rep. 12:2098–2106. 2015.PubMed/NCBI View Article : Google Scholar
10	Wang C, Bian Z, Wei D and Zhang JG: miR-29b regulates migration of human breast cancer cells. Mol Cell Biochem. 352:197–207. 2011.PubMed/NCBI View Article : Google Scholar
11	Cortez MA, Nicoloso MS, Shimizu M, Rossi S, Gopisetty G, Molina JR, Carlotti C Jr, Tirapelli D, Neder L, Brassesco MS, et al: miR-29b and miR-125a regulate podoplanin and suppress invasion in glioblastoma. Genes Chromosomes Cancer. 49:981–990. 2010.PubMed/NCBI View Article : Google Scholar
12	Garzon R, Heaphy CE, Havelange V, Fabbri M, Volinia S, Tsao T, Zanesi N, Kornblau SM, Marcucci G, Calin GA, et al: MicroRNA 29b functions in acute myeloid leukemia. Blood. 114:5331–5341. 2009.PubMed/NCBI View Article : Google Scholar
13	Zeng Q, Wang Y, Gao J, Yan Z, Li Z, Zou X, Li Y, Wang J and Guo Y: miR-29b-3p regulated osteoblast differentiation via regulating IGF-1 secretion of mechanically stimulated osteocytes. Cell Mol Biol Lett. 24(11)2019.PubMed/NCBI View Article : Google Scholar
14	McCall MN, Bolstad BM and Irizarry RA: Frozen robust multiarray analysis (fRMA). Biostatistics. 11:242–253. 2010.PubMed/NCBI View Article : Google Scholar
15	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
16	Friedman RC, Farh KK, Burge CB and Bartel DP: Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 19:92–105. 2009.PubMed/NCBI View Article : Google Scholar
17	Szklarczyk D, Morris JH, Cook H, Kuhn M, Wyder S, Simonovic M, Santos A, Doncheva NT, Roth A, Bork P, et al: The STRING database in 2017: Quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res. 45:D362–D368. 2017.PubMed/NCBI View Article : Google Scholar
18	Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J, Puigserver P, Carlsson E, Ridderstrale M, Laurila E, et al: PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet. 34:267–273. 2003.PubMed/NCBI View Article : Google Scholar
19	Mathavan N, Turunen MJ, Tägil M and Isaksson H: Characterising bone material composition and structure in the ovariectomized (OVX) rat model of osteoporosis. Calcif Tissue Int. 97:134–144. 2015.PubMed/NCBI View Article : Google Scholar
20	Rossi M, Pitari MR, Amodio N, Di Martino MT, Conforti F, Leone E, Botta C, Paolino FM, Del Giudice T, Iuliano E, et al: miR-29b negatively regulates human osteoclastic cell differentiation and function: Implications for the treatment of multiple myeloma-related bone disease. J Cell Physiol. 228:1506–1515. 2013.PubMed/NCBI View Article : Google Scholar
21	Zhang B, Shetti D, Fan C and Wei K: miR-29b-3p promotes progression of MDA-MB-231 triple-negative breast cancer cells through downregulating TRAF3. Biol Res. 52(38)2019.PubMed/NCBI View Article : Google Scholar
22	Yu F, Chen B, Dong P and Zheng J: HOTAIR epigenetically modulates PTEN expression via microRNA-29b: A novel mechanism in regulation of liver fibrosis. Mol Ther. 25:205–217. 2017.PubMed/NCBI View Article : Google Scholar
23	Yan B, Guo Q, Fu FJ, Wang Z, Yin Z, Wei YB and Yang JR: The role of miR-29b in cancer: Regulation, function, and signaling. Onco Targets Ther. 8:539–548. 2015.PubMed/NCBI View Article : Google Scholar
24	Dong Y, Liang G, Yuan B, Yang C, Gao R and Zhou X: MALAT1 promotes the proliferation and metastasis of osteosarcoma cells by activating the PI3K/Akt pathway. Tumour Biol. 36:1477–1486. 2015.PubMed/NCBI View Article : Google Scholar
25	Jin Y, Chen W, Yang H, Yan Z, Lai Z, Feng J, Peng J and Lin J: Scutellaria barbata D: Don inhibits migration and invasion of colorectal cancer cells via suppression of PI3K/AKT and TGF-β/Smad signaling pathways. Exp Ther Med. 14:5527–5534. 2017.PubMed/NCBI View Article : Google Scholar
26	Wu S, Wang Y, Yuan Z, Wang S, Du H, Liu X, Wang Q and Zhu X: Human adiposederived mesenchymal stem cells promote breast cancer MCF7 cell epithelialmesenchymal transition by cross interacting with the TGFβ/Smad and PI3K/AKT signaling pathways. Mol Med Rep. 19:177–186. 2019.PubMed/NCBI View Article : Google Scholar