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Osteoporosis International

Erschienen in:

01.04.2016 | Original Article

Glucocorticoids impair bone formation of bone marrow stromal stem cells by reciprocally regulating microRNA-34a-5p

verfasst von: H. Kang, H. Chen, P. Huang, J. Qi, N. Qian, L. Deng, L. Guo

Erschienen in: Osteoporosis International | Ausgabe 4/2016

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Abstract

Summary

The inhibitory effects of glucocorticoids (GCs) on bone marrow stromal stem cell (BMSC) proliferation and osteoblastic differentiation are an important pathway through which GCs decrease bone formation. We found that microRNA-34a-5p was a critical player in dexamethasone (Dex)-inhibited BMSC proliferation and osteogenic differentiation. MicroRNA-34a-5p might be used as a therapeutic target for GC-impaired bone formation.

Introduction

The inhibitory effects of glucocorticoids (GCs) on bone marrow stromal stem cell (BMSC) proliferation and osteoblastic differentiation are an important pathway through which GCs decrease bone formation. The mechanisms of this process are still not completely understood. Recent studies implicated an important role of microRNAs in GC-mediated responses in various cellular processes, including cell proliferation and differentiation. Therefore, we hypothesized that these regulatory molecules might be implicated in the process of GC-decreased BMSC proliferation and osteoblastic differentiation.

Methods

Western blot, quantitative real-time PCR, and cell proliferation and osteoblastic differentiation assays were employed to investigate the role of microRNAs in GC-inhibited BMSC proliferation and osteoblastic differentiation.

Results

We found that microRNA-34a-5p was reciprocally regulated by Dex during the process of BMSC proliferation and osteoblastic differentiation. Furthermore, we confirmed that microRNA-34a-5p was a critical player in Dex-inhibited BMSC proliferation and osteogenic differentiation. Mechanistic studies showed that Dex inhibited BMSC proliferation by microRNA-34a-5p targeting cell cycle factors, including CDK4, CDK6, and Cyclin D1. Furthermore, downregulation of microRNA-34a-5p by Dex leads to Notch signaling activation, resulting in inhibition of BMSC osteogenic differentiation.

Conclusions

These results showed that microRNA-34a-5p, a crucial regulator for BMSC proliferation and osteogenic differentiation, might be used as a therapeutic target for GC-impaired bone formation.

Shi C, Qi J, Huang P et al (2014) MicroRNA-17/20a inhibits glucocorticoid-induced osteoclast differentiation and function through targeting RANKL expression in osteoblast cells. Bone 67–75

Tait AS, Butts CL, Sternberg EM (2008) The role of glucocorticoids and progestins in inflammatory, autoimmune, and infectious disease. J Leukoc Biol 84:924–931CrossRefPubMedPubMedCentral

Kondo T, Kitazawa R, Yamaguchi A, Kitazawa S (2008) Dexamethasone promotes osteoclastogenesis by inhibiting osteoprotegerin through multiple levels. J Cell Biochem 103:335–345CrossRefPubMed

Weinstein RS, Jilka RL, Parfitt AM, Manolagas SC (1998) Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone. J Clin Invest 102:274–282CrossRefPubMedPubMedCentral

Henneicke H, Gasparini SJ, Brennan-Speranza TC, Zhou H, Seibel MJ (2014) Glucocorticoids and bone: local effects and systemic implications. Trends Endocrinol Metab TEM 25:197–211CrossRefPubMed

Lemaire V, Tobin FL, Greller LD, Cho CR, Suva LJ (2004) Modeling the interactions between osteoblast and osteoclast activities in bone remodeling. J Theor Biol 229:293–309CrossRefPubMed

Sacchetti B, Funari A, Michienzi S et al (2007) Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell 131:324–336CrossRefPubMed

Mitra R (2011) Adverse effects of corticosteroids on bone metabolism: a review. PM R 3:466–471, quiz 471 CrossRefPubMed

Couzin J (2007) Genetics. Erasing microRNAs reveals their powerful punch. Science 316:530CrossRefPubMed

10.

Zamore PD, Haley B (2005) Ribo-gnome: the big world of small RNAs. Science 309:1519–1524CrossRefPubMed

11.

Zeng Y (2006) Principles of micro-RNA production and maturation. Oncogene 25:6156–6162CrossRefPubMed

12.

Guo L, Xu J, Qi J, Zhang L, Wang J, Liang J, Qian N, Zhou H, Wei L, Deng L (2013) MicroRNA-17-92a upregulation by estrogen leads to Bim targeting and inhibition of osteoblast apoptosis. J Cell Sci 126:978–988CrossRefPubMed

13.

Shi C, Huang P, Kang H, Hu B, Qi J, Jiang M, Zhou H, Guo L, Deng L (2015) Glucocorticoid inhibits cell proliferation in differentiating osteoblasts by microRNA-199a targeting of WNT signaling. J Mol Endocrinol 54:325–337CrossRefPubMed

14.

Shi C, Qi J, Huang P et al (2014) MicroRNA-17/20a inhibits glucocorticoid-induced osteoclast differentiation and function through targeting RANKL expression in osteoblast cells. Bone 68:67–75CrossRefPubMed

15.

Chen L, Holmstrom K, Qiu W, Ditzel N, Shi K, Hokland L, Kassem M (2014) MicroRNA-34a inhibits osteoblast differentiation and in vivo bone formation of human stromal stem cells. Stem Cells 32:902–912CrossRefPubMed

16.

Pan W, Wang H, Jianwei R, Ye Z (2014) MicroRNA-27a promotes proliferation, migration and invasion by targeting MAP2K4 in human osteosarcoma cells. Cell Physiol Biochem 33:402–412CrossRefPubMed

17.

Eskildsen T, Taipaleenmaki H, Stenvang J, Abdallah BM, Ditzel N, Nossent AY, Bak M, Kauppinen S, Kassem M (2011) MicroRNA-138 regulates osteogenic differentiation of human stromal (mesenchymal) stem cells in vivo. Proc Natl Acad Sci U S A 108:6139–6144CrossRefPubMedPubMedCentral

18.

Li J, Zhang N, Huang X, Xu J, Fernandes JC, Dai K, Zhang X (2013) Dexamethasone shifts bone marrow stromal cells from osteoblasts to adipocytes by C/EBPalpha promoter methylation. Cell Death Dis 4, e832CrossRefPubMedPubMedCentral

19.

Chiu LH, Lai WF, Chang SF, Wong CC, Fan CY, Fang CL, Tsai YH (2014) The effect of type II collagen on MSC osteogenic differentiation and bone defect repair. Biomaterials 35:2680–2691CrossRefPubMed

20.

Dore LC, Amigo JD, Dos Santos CO et al (2008) A GATA-1-regulated microRNA locus essential for erythropoiesis. Proc Natl Acad Sci U S A 105:3333–3338CrossRefPubMedPubMedCentral

21.

Kong X, Yu J, Bi J et al (2015) Glucocorticoids transcriptionally regulate miR-27b expression promoting body fat accumulation via suppressing the browning of white adipose tissue. Diabetes 64:393–404CrossRefPubMed

22.

Ko JY, Chuang PC, Chen MW, Ke HC, Wu SL, Chang YH, Chen YS, Wang FS (2013) MicroRNA-29a ameliorates glucocorticoid-induced suppression of osteoblast differentiation by regulating beta-catenin acetylation. Bone 57:468–475CrossRefPubMed

23.

Wang FS, Chuang PC, Lin CL, Chen MW, Ke HJ, Chang YH, Chen YS, Wu SL, Ko JY (2013) MicroRNA-29a protects against glucocorticoid-induced bone loss and fragility in rats by orchestrating bone acquisition and resorption. Arthritis Rheum 65:1530–1540CrossRefPubMed

24.

Wei J, Shi Y, Zheng L, Zhou B, Inose H, Wang J, Guo XE, Grosschedl R, Karsenty G (2012) miR-34s inhibit osteoblast proliferation and differentiation in the mouse by targeting SATB2. J Cell Biol 197:509–521CrossRefPubMedPubMedCentral

25.

Stahn C, Buttgereit F (2008) Genomic and nongenomic effects of glucocorticoids. Nat Clin Pract Rheumatol 4:525–533CrossRefPubMed

26.

Wei N, Yu Y, Joshi V, Schmidt T, Qian F, Salem AK, Stanford C, Hong L (2013) Glucocorticoid receptor antagonist and siRNA prevent senescence of human bone marrow mesenchymal stromal cells in vitro. Cell Tissue Res 354:461–470CrossRefPubMedPubMedCentral

27.

De Iudicibus S, Lucafo M, Martelossi S, Pierobon C, Ventura A, Decorti G (2013) MicroRNAs as tools to predict glucocorticoid response in inflammatory bowel diseases. World J Gastroenterol 19:7947–7954CrossRefPubMedPubMedCentral

28.

Honjo T (1996) The shortest path from the surface to the nucleus: RBP-J kappa/Su(H) transcription factor. Genes Cells 1:1–9CrossRefPubMed

29.

Bai S, Kopan R, Zou W, Hilton MJ, Ong CT, Long F, Ross FP, Teitelbaum SL (2008) NOTCH1 regulates osteoclastogenesis directly in osteoclast precursors and indirectly via osteoblast lineage cells. J Biol Chem 283:6509–6518CrossRefPubMed

30.

Salie R, Kneissel M, Vukevic M, Zamurovic N, Kramer I, Evans G, Gerwin N, Mueller M, Kinzel B, Susa M (2010) Ubiquitous overexpression of Hey1 transcription factor leads to osteopenia and chondrocyte hypertrophy in bone. Bone 46:680–694CrossRefPubMed

31.

Deregowski V, Gazzerro E, Priest L, Rydziel S, Canalis E (2006) Notch 1 overexpression inhibits osteoblastogenesis by suppressing Wnt/beta-catenin but not bone morphogenetic protein signaling. J Biol Chem 281:6203–6210CrossRefPubMed

32.

Tezuka K, Yasuda M, Watanabe N, Morimura N, Kuroda K, Miyatani S, Hozumi N (2002) Stimulation of osteoblastic cell differentiation by Notch. J Bone Miner Res 17:231–239CrossRefPubMed

33.

Xu N, Liu H, Qu F, Fan J, Mao K, Yin Y, Liu J, Geng Z, Wang Y (2013) Hypoxia inhibits the differentiation of mesenchymal stem cells into osteoblasts by activation of Notch signaling. Exp Mol Pathol 94:33–39CrossRefPubMed

34.

Zhu F, Sweetwyne MT, Hankenson KD (2013) PKCdelta is required for Jagged-1 induction of human mesenchymal stem cell osteogenic differentiation. Stem Cells 31:1181–1192CrossRefPubMed

Titel: Glucocorticoids impair bone formation of bone marrow stromal stem cells by reciprocally regulating microRNA-34a-5p
verfasst von: H. Kang
H. Chen
P. Huang
J. Qi
N. Qian
L. Deng
L. Guo
Publikationsdatum: 01.04.2016
Verlag: Springer London
Erschienen in: Osteoporosis International / Ausgabe 4/2016
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-015-3381-x

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Glucocorticoids impair bone formation of bone marrow stromal stem cells by reciprocally regulating microRNA-34a-5p

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Summary

Introduction

Methods

Results

Conclusions

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