Circulating osteocyte‑derived exosomes contain miRNAs which are enriched in exosomes from MLO-Y4 cells

Sato,Mari; Suzuki,Tomohide; Kawano,Mitsuoki; Tamura,Masato

doi:10.3892/br.2016.824

Circulating osteocyte‑derived exosomes contain miRNAs which are enriched in exosomes from MLO-Y4 cells

Authors:
- Mari Sato
- Tomohide Suzuki
- Mitsuoki Kawano
- Masato Tamura
View Affiliations

Affiliations: Department of Biochemistry and Molecular Biology, Graduate School of Dental Medicine, Hokkaido University, Sapporo 060‑8586, Japan, Hematology Division, Department of Medicine, Kobe University Graduate School of Medicine, Kobe 650‑0017, Japan, Department of Applied Life Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956‑8603, Japan
Published online on: December 5, 2016 https://doi.org/10.3892/br.2016.824
Pages: 223-231

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

Signaling molecules produced by osteocytes have been proposed to serve as soluble factors that contribute to bone remodeling, as well as to homeostasis of other organs. However, to the best of our knowledge, there are currently no studies investigating the role of osteocyte‑secreted exosomes. In the present study, ablation of osteocytes in mice [osteocyte‑less (OL)] was used to examine the microRNA (miRNA) levels of plasma‑circulating exosomes. In order to investigate the function of osteocyte‑secreted exosomes, exosomes derived from MLO‑Y4 cells were extracted and their miRNA expression levels were examined using miRNA array analysis and deep sequencing. Comparison of miRNA expression levels between plasma exosomes from OL mouse plasma and MLO‑Y4‑derived exosomes revealed that decreases in the number of miRNAs from exosomes circulating in the OL mouse plasma may be caused by a decrease in secretion of exosomes from osteocytes. These results suggest that osteocytes secrete exosomes containing characterized miRNAs and then circulate in the blood, and may thus transfer their components, including miRNAs, to recipient cells where they function as signaling molecules in other organs and/or tissues to regulate biological responses.

View Figures

View References

1	Bonewald LF: The amazing osteocyte. J Bone Miner Res. 26:229–238. 2011. View Article : Google Scholar : PubMed/NCBI
2	Schaffler MB, Cheung WY, Majeska R and Kennedy O: Osteocytes: Master orchestrators of bone. Calcif Tissue Int. 94:5–24. 2014. View Article : Google Scholar : PubMed/NCBI
3	Dallas SL, Prideaux M and Bonewald LF: The osteocyte: An endocrine cell and more. Endocr Rev. 34:658–690. 2013. View Article : Google Scholar : PubMed/NCBI
4	Quarles LD: Skeletal secretion of FGF-23 regulates phosphate and vitamin D metabolism. Nat Rev Endocrinol. 8:276–286. 2012. View Article : Google Scholar : PubMed/NCBI
5	Sato M, Asada N, Kawano Y, Wakahashi K, Minagawa K, Kawano H, Sada A, Ikeda K, Matsui T and Katayama Y: Osteocytes regulate primary lymphoid organs and fat metabolism. Cell Metab. 18:749–758. 2013. View Article : Google Scholar : PubMed/NCBI
6	Colombo M, Raposo G and Théry C: Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol. 30:255–289. 2014. View Article : Google Scholar : PubMed/NCBI
7	Vlassov AV, Magdaleno S, Setterquist R and Conrad R: Exosomes: Current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochim Biophys Acta. 1820:940–948. 2012. View Article : Google Scholar : PubMed/NCBI
8	Salido-Guadarrama I, Romero-Cordoba S, Peralta-Zaragoza O, Hidalgo-Miranda A and Rodríguez-Dorantes M: MicroRNAs transported by exosomes in body fluids as mediators of intercellular communication in cancer. Onco Targets Ther. 7:1327–1338. 2014.PubMed/NCBI
9	Simons M and Raposo G: Exosomes - vesicular carriers for intercellular communication. Curr Opin Cell Biol. 21:575–581. 2009. View Article : Google Scholar : PubMed/NCBI
10	Stoorvogel W: Functional transfer of microRNA by exosomes. Blood. 119:646–648. 2012. View Article : Google Scholar : PubMed/NCBI
11	Williams AE: Functional aspects of animal microRNAs. Cell Mol Life Sci. 65:545–562. 2008. View Article : Google Scholar : PubMed/NCBI
12	Sayed D and Abdellatif M: MicroRNAs in development and disease. Physiol Rev. 91:827–887. 2011. View Article : Google Scholar : PubMed/NCBI
13	Bushati N and Cohen SM: microRNA functions. Annu Rev Cell Dev Biol. 23:175–205. 2007. View Article : Google Scholar : PubMed/NCBI
14	Huntzinger E and Izaurralde E: Gene silencing by microRNAs: Contributions of translational repression and mRNA decay. Nat Rev Genet. 12:99–110. 2011. View Article : Google Scholar : PubMed/NCBI
15	Montecalvo A, Larregina AT, Shufesky WJ, Stolz DB, Sullivan ML, Karlsson JM, Baty CJ, Gibson GA, Erdos G, Wang Z, et al: Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes. Blood. 119:756–766. 2012. View Article : Google Scholar : PubMed/NCBI
16	van Balkom BW, de Jong OG, Smits M, Brummelman J, den Ouden K, de Bree PM, van Eijndhoven MA, Pegtel DM, Stoorvogel W, Würdinger T and Verhaar MC: Endothelial cells require miR-214 to secrete exosomes that suppress senescence and induce angiogenesis in human and mouse endothelial cells. Blood. 121:3997–4006, S1-S15. 2013. View Article : Google Scholar : PubMed/NCBI
17	Tatsumi S, Ishii K, Amizuka N, Li M, Kobayashi T, Kohno K, Ito M, Takeshita S and Ikeda K: Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction. Cell Metab. 5:464–475. 2007. View Article : Google Scholar : PubMed/NCBI
18	Kato Y, Windle JJ, Koop BA, Mundy GR and Bonewald LF: Establishment of an osteocyte-like cell line, MLO-Y4. J Bone Miner Res. 12:2014–2023. 1997. View Article : Google Scholar : PubMed/NCBI
19	Tamura M, Sato MM and Nashimoto M: Regulation of CXCL12 expression by canonical Wnt signaling in bone marrow stromal cells. Int J Biochem Cell Biol. 43:760–767. 2011. View Article : Google Scholar : PubMed/NCBI
20	Sato M and Katayama Y: Osteocytes and Homeostasis of Remote Organs: Bone-Buried Osteocytes Talk to Remote Organs. Curr Osteoporos Rep. 13:193–197. 2015. View Article : Google Scholar : PubMed/NCBI
21	Ogawa M and Nishikawa S, Ikuta K, Yamamura F, Naito M, Takahashi K and Nishikawa S: B cell ontogeny in murine embryo studied by a culture system with the monolayer of a stromal cell clone, ST2: B cell progenitor develops first in the embryonal body rather than in the yolk sac. EMBO J. 7:1337–1343. 1988.PubMed/NCBI
22	Otsuka E, Yamaguchi A, Hirose S and Hagiwara H: Characterization of osteoblastic differentiation of stromal cell line ST2 that is induced by ascorbic acid. Am J Physiol. 277:C132–C138. 1999.PubMed/NCBI
23	Liu CG, Calin GA, Meloon B, Gamliel N, Sevignani C, Ferracin M, Dumitru CD, Shimizu M, Zupo S, Dono M, et al: An oligonucleotide microchip for genome-wide microRNA profiling in human and mouse tissues. Proc Natl Acad Sci USA. 101:9740–9744. 2004. View Article : Google Scholar : PubMed/NCBI
24	Kogianni G, Mann V and Noble BS: Apoptotic bodies convey activity capable of initiating osteoclastogenesis and localized bone destruction. J Bone Miner Res. 23:915–927. 2008. View Article : Google Scholar : PubMed/NCBI
25	Vemuganti R, Silva VR, Mehta SL and Hazell AS: Acute liver failure-induced hepatic encephalopathy s associated with changes in microRNA expression rofiles in cerebral cortex of the mouse [corrected]. Metab Brain Dis. 29:891–899. 2014. View Article : Google Scholar : PubMed/NCBI
26	Tang X, Muniappan L, Tang G and Ozcan S: Identification of glucose-regulated miRNAs from pancreatic {beta} cells reveals a role for miR-30d in insulin transcription. RNA. 15:287–293. 2009. View Article : Google Scholar : PubMed/NCBI
27	Xie H, Lim B and Lodish HF: MicroRNAs induced during adipogenesis that accelerate fat cell development are downregulated in obesity. Diabetes. 58:1050–1057. 2009. View Article : Google Scholar : PubMed/NCBI
28	Williams MD and Mitchell GM: MicroRNAs in insulin resistance and obesity. Exp Diabetes Res. 2012:4846962012. View Article : Google Scholar : PubMed/NCBI
29	Kamioka H, Honjo T and Takano-Yamamoto T: A three-dimensional distribution of osteocyte processes revealed by the combination of confocal laser scanning microscopy and differential interference contrast microscopy. Bone. 28:145–149. 2001. View Article : Google Scholar : PubMed/NCBI
30	Chen TS and Lim SK: Measurement of precursor miRNA in exosomes from human ESC-derived mesenchymal stem cells. Methods Mol Biol. 1024:69–86. 2013. View Article : Google Scholar : PubMed/NCBI
31	Melo SA, Sugimoto H, O'Connell JT, Kato N, Villanueva A, Vidal A, Qiu L, Vitkin E, Perelman LT, Melo CA, et al: Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis. Cancer Cell. 26:707–721. 2014. View Article : Google Scholar : PubMed/NCBI
32	Lee HK, Finniss S, Cazacu S, Xiang C and Brodie C: Mesenchymal stem cells deliver exogenous miRNAs to neural cells and induce their differentiation and glutamate transporter expression. Stem Cells Dev. 23:2851–2861. 2014. View Article : Google Scholar : PubMed/NCBI
33	Mittelbrunn M and Sánchez-Madrid F: Intercellular communication: Diverse structures for exchange of genetic information. Nat Rev Mol Cell Biol. 13:328–335. 2012.PubMed/NCBI