MiRNA-132-3p Inhibits Osteoblast Differentiation by Targeting Ep300 in Simulated Microgravity

Overview

Journal Sci Rep

Specialty Science

Date 2015 Dec 22

PMID 26686902

Citations 51

Authors

Zebing Hu

Yixuan Wang

Zhongyang Sun

Han Wang

Hua Zhou

Lianchang Zhang

Shu Zhang

Xinsheng Cao

Affiliations

Soon will be listed here.

Abstract

Recent studies have demonstrated that miRNAs can play important roles in osteoblast differentiation and bone formation. However, the function of miRNAs in bone loss induced by microgravity remains unclear. In this study, we investigated the differentially expressed miRNAs in both the femur tissues of hindlimb unloading rats and primary rat osteoblasts (prOB) exposed to simulated microgravity. Specifically, miR-132-3p was found up-regulated and negatively correlated with osteoblast differentiation. Overexpression of miR-132-3p significantly inhibited prOB differentiation, whereas inhibition of miR-132-3p function yielded an opposite effect. Furthermore, silencing of miR-132-3p expression effectively attenuated the negative effects of simulated microgravity on prOB differentiation. Further experiments confirmed that E1A binding protein p300 (Ep300), a type of histone acetyltransferase important for Runx2 activity and stability, was a direct target of miR-132-3p. Up-regulation of miR-132-3p by simulated microgravity could inhibit osteoblast differentiation in part by decreasing Ep300 protein expression, which, in turn, resulted in suppression of the activity and acetylation of Runx2, a key regulatory factor of osteoblast differentiation. Taken together, our findings are the first to demonstrate that miR-132-3p can inhibit osteoblast differentiation and participate in the regulation of bone loss induced by simulated microgravity, suggesting a potential target for counteracting decreases in bone formation.

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References

Sun Z, Cao X, Hu Z, Zhang L, Wang H, Zhou H . MiR-103 inhibits osteoblast proliferation mainly through suppressing Cav1.2 expression in simulated microgravity. Bone. 2015; 76:121-8. DOI: 10.1016/j.bone.2015.04.006. View

He L, Hannon G . MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004; 5(7):522-31. DOI: 10.1038/nrg1379. View

Wang H, Ach R, Curry B . Direct and sensitive miRNA profiling from low-input total RNA. RNA. 2006; 13(1):151-9. PMC: 1705746. DOI: 10.1261/rna.234507. View

Saxena R, Pan G, McDonald J . Osteoblast and osteoclast differentiation in modeled microgravity. Ann N Y Acad Sci. 2007; 1116:494-8. DOI: 10.1196/annals.1402.033. View

Gronroos E, Hellman U, Heldin C, Ericsson J . Control of Smad7 stability by competition between acetylation and ubiquitination. Mol Cell. 2002; 10(3):483-93. DOI: 10.1016/s1097-2765(02)00639-1. View

Ohshima H . [Secondary osteoporosis UPDATE. Bone loss due to bed rest and human space flight study]. Clin Calcium. 2010; 20(5):709-16. DOI: CliCa1005709716. View

Tsao Y, Goodwin T, Wolf D, Spaulding G . Responses of gravity level variations on the NASA/JSC bioreactor system. Physiologist. 1992; 35(1 Suppl):S49-50. View

Zhang J, Fu W, He M, Xie W, Lv Q, Wan G . MiRNA-20a promotes osteogenic differentiation of human mesenchymal stem cells by co-regulating BMP signaling. RNA Biol. 2011; 8(5):829-38. DOI: 10.4161/rna.8.5.16043. View

Lian J, Stein G, van Wijnen A, Stein J, Hassan M, Gaur T . MicroRNA control of bone formation and homeostasis. Nat Rev Endocrinol. 2012; 8(4):212-27. PMC: 3589914. DOI: 10.1038/nrendo.2011.234. View

10.

Gao J, Yang T, Han J, Yan K, Qiu X, Zhou Y . MicroRNA expression during osteogenic differentiation of human multipotent mesenchymal stromal cells from bone marrow. J Cell Biochem. 2011; 112(7):1844-56. DOI: 10.1002/jcb.23106. View

11.

Globus R, Bikle D, Morey-Holton E . Effects of simulated weightlessness on bone mineral metabolism. Endocrinology. 1984; 114(6):2264-70. DOI: 10.1210/endo-114-6-2264. View

12.

Hahn M, Vogel M, Delling G . Trabecular bone pattern factor--a new parameter for simple quantification of bone microarchitecture. Bone. 1992; 13(4):327-30. DOI: 10.1016/8756-3282(92)90078-b. View

13.

Owen T, Aronow M, Shalhoub V, Barone L, Wilming L, Tassinari M . Progressive development of the rat osteoblast phenotype in vitro: reciprocal relationships in expression of genes associated with osteoblast proliferation and differentiation during formation of the bone extracellular matrix. J Cell Physiol. 1990; 143(3):420-30. DOI: 10.1002/jcp.1041430304. View

14.

Sun L, Fan Y, Li D, Zhao F, Xie T, Yang X . Evaluation of the mechanical properties of rat bone under simulated microgravity using nanoindentation. Acta Biomater. 2009; 5(9):3506-11. DOI: 10.1016/j.actbio.2009.04.042. View

15.

Martin R . Effects of simulated weightlessness on bone properties in rats. J Biomech. 1990; 23(10):1021-9. DOI: 10.1016/0021-9290(90)90317-v. View

16.

Bae Y, Yang T, Zeng H, Campeau P, Chen Y, Bertin T . miRNA-34c regulates Notch signaling during bone development. Hum Mol Genet. 2012; 21(13):2991-3000. PMC: 3373245. DOI: 10.1093/hmg/dds129. View

17.

Jun J, Yoon W, Seo S, Woo K, Kim G, Ryoo H . BMP2-activated Erk/MAP kinase stabilizes Runx2 by increasing p300 levels and histone acetyltransferase activity. J Biol Chem. 2010; 285(47):36410-9. PMC: 2978570. DOI: 10.1074/jbc.M110.142307. View

18.

Vico L, Chappard D, Palle S, Bakulin A, Novikov V, Alexandre C . Trabecular bone remodeling after seven days of weightlessness exposure (BIOCOSMOS 1667). Am J Physiol. 1988; 255(2 Pt 2):R243-7. DOI: 10.1152/ajpregu.1988.255.2.R243. View

19.

Sun Z, Cao X, Zhang Z, Hu Z, Zhang L, Wang H . Simulated microgravity inhibits L-type calcium channel currents partially by the up-regulation of miR-103 in MC3T3-E1 osteoblasts. Sci Rep. 2015; 5:8077. PMC: 4308706. DOI: 10.1038/srep08077. View

20.

Zhang Z, Zhang H, Kang Y, Sheng P, Ma Y, Yang Z . miRNA expression profile during osteogenic differentiation of human adipose-derived stem cells. J Cell Biochem. 2012; 113(3):888-98. DOI: 10.1002/jcb.23418. View