Skip to main content

Advertisement

SpringerLink
Log in

Extracellular vesicle-mediated bone metabolism in the bone microenvironment

  • Review Article
  • Published:
Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

Extracellular vesicles (EVs) are phospholipid membrane-enclosed entities containing specific proteins, RNA, miRNA, and lncRNA. EVs are released by various cells and play a vital role in cell communication by transferring their contents from the host cells to the recipient cells. The role of EVs has been characterized in a wide range of physiological and pathophysiological processes. In this context, we highlight recent advances in our understanding of the regulatory effects of EVs, with a focus on bone metabolism and the bone microenvironment. The roles of EVs in cell communication among bone-related cells, stem cells, tumor cells, and other cells under physiological or pathological conditions are also discussed. In addition, promising applications for EVs in treating bone-related diseases are proposed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Qin Y, Sun R, Wu C, Wang L, Zhang C (2016) Exosome: a novel approach to stimulate bone regeneration through regulation of osteogenesis and angiogenesis. Int J Mol Sci 17:712. doi:10.3390/ijms17050712

    Article  PubMed Central  Google Scholar 

  2. Nolte-’t Hoen E, Cremer T, Gallo RC, Margolis LB (2016) Extracellular vesicles and viruses: are they close relatives?. Proc Natl Acad Sci USA 113:9155–9161. doi:10.1073/pnas.1605146113

    Article  PubMed  PubMed Central  Google Scholar 

  3. Morhayim J, Baroncelli M, van Leeuwen JP (2014) Extracellular vesicles: specialized bone messengers. Arch Biochem Biophys 561:38–45. doi:10.1016/j.abb.2014.05.011

    Article  CAS  PubMed  Google Scholar 

  4. Cocucci E, Racchetti G, Meldolesi J (2009) Shedding microvesicles: artefacts no more. Trends Cell Biol 19:43–51. doi:10.1016/j.tcb.2008.11.003

    Article  CAS  PubMed  Google Scholar 

  5. Simons M, Raposo G (2009) Exosomes–vesicular carriers for intercellular communication. Curr Opin Cell Biol 21:575–581. doi:10.1016/j.ceb.2009.03.007

    Article  CAS  PubMed  Google Scholar 

  6. Hristov M, Erl W, Linder S, Weber PC (2004) Apoptotic bodies from endothelial cells enhance the number and initiate the differentiation of human endothelial progenitor cells in vitro. Blood 104:2761–2766. doi:10.1182/blood-2003-10-3614

    Article  CAS  PubMed  Google Scholar 

  7. Camussi G, Deregibus MC, Bruno S, Cantaluppi V, Biancone L (2010) Exosomes/microvesicles as a mechanism of cell-to-cell communication. Kidney Int 78:838–848. doi:10.1038/ki.2010.278

    Article  CAS  PubMed  Google Scholar 

  8. van der Pol E, Boing AN, Harrison P, Sturk A, Nieuwland R (2012) Classification, functions, and clinical relevance of extracellular vesicles. Pharmacol Rev 64:676–705. doi:10.1124/pr.112.005983

    Article  PubMed  Google Scholar 

  9. Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9:654–659. doi:10.1038/ncb1596

    Article  CAS  PubMed  Google Scholar 

  10. Hannafon BN, Carpenter KJ, Berry WL, Janknecht R, Dooley WC, Ding WQ (2015) Exosome-mediated microRNA signaling from breast cancer cells is altered by the anti-angiogenesis agent docosahexaenoic acid (DHA). Mol Cancer 14:133. doi:10.1186/s12943-015-0400-7

    Article  PubMed  PubMed Central  Google Scholar 

  11. Shurtleff MJ, Temoche-Diaz MM, Karfilis KV, Ri S, Schekman R (2016) Y-box protein 1 is required to sort microRNAs into exosomes in cells and in a cell-free reaction. eLife. doi:10.7554/eLife.19276

    PubMed  PubMed Central  Google Scholar 

  12. Nakamachi Y, Kawano S, Takenokuchi M, Nishimura K, Sakai Y, Chin T, Saura R, Kurosaka M, Kumagai S (2009) MicroRNA-124a is a key regulator of proliferation and monocyte chemoattractant protein 1 secretion in fibroblast-like synoviocytes from patients with rheumatoid arthritis. Arthritis Rheum 60:1294–1304. doi:10.1002/art.24475

    Article  PubMed  Google Scholar 

  13. Wilusz JE, Sunwoo H, Spector DL (2009) Long noncoding RNAs: functional surprises from the RNA world. Genes Dev 23:1494–1504. doi:10.1101/gad.1800909

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Sims NA, Walsh NC (2012) Intercellular cross-talk among bone cells: new factors and pathways. Curr Osteoporos Rep 10:109–117. doi:10.1007/s11914-012-0096-1

    Article  PubMed  Google Scholar 

  15. Chiu YH, Ritchlin CT (2016) DC-STAMP: a key regulator in osteoclast differentiation. J Cell Physiol 231:2402–2407. doi:10.1002/jcp.25389

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Deng L, Wang Y, Peng Y, Wu Y, Ding Y, Jiang Y, Shen Z, Fu Q (2015) Osteoblast-derived microvesicles: a novel mechanism for communication between osteoblasts and osteoclasts. Bone 79:37–42. doi:10.1016/j.bone.2015.05.022

    Article  CAS  PubMed  Google Scholar 

  17. Bronisz A, Godlewski J, Chiocca EA (2016) Extracellular vesicles and microRNAs: their role in tumorigenicity and therapy for brain tumors. Cell Mol Neurobiol 36:361–376. doi:10.1007/s10571-015-0293-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kosaka N, Yoshioka Y, Fujita Y, Ochiya T (2016) Versatile roles of extracellular vesicles in cancer. J Clin Investig 126:1163–1172. doi:10.1172/JCI81130

    Article  PubMed  PubMed Central  Google Scholar 

  19. Ciardiello C, Cavallini L, Spinelli C, Yang J, Reis-Sobreiro M, de Candia P, Minciacchi VR, Di Vizio D (2016) Focus on extracellular vesicles: new frontiers of cell-to-cell communication in cancer. Int J Mol Sci 17:175. doi:10.3390/ijms17020175

    Article  PubMed  PubMed Central  Google Scholar 

  20. Lopatina T, Gai C, Deregibus MC, Kholia S, Camussi G (2016) Cross talk between cancer and mesenchymal stem cells through extracellular vesicles carrying nucleic acids. Front Oncol 6:125. doi:10.3389/fonc.2016.00125

    Article  PubMed  PubMed Central  Google Scholar 

  21. Desrochers LM, Antonyak MA, Cerione RA (2016) Extracellular vesicles: satellites of information transfer in cancer and stem cell biology. Dev Cell 37:301–309. doi:10.1016/j.devcel.2016.04.019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Kramer-Albers EM, Hill AF (2016) Extracellular vesicles: interneural shuttles of complex messages. Curr Opin Neurobiol 39:101–107. doi:10.1016/j.conb.2016.04.016

    Article  PubMed  Google Scholar 

  23. Zappulli V, Friis KP, Fitzpatrick Z, Maguire CA, Breakefield XO (2016) Extracellular vesicles and intercellular communication within the nervous system. J Clin Investig 126:1198–1207. doi:10.1172/JCI81134

    Article  PubMed  PubMed Central  Google Scholar 

  24. Teixeira JH, Silva AM, Almeida MI, Barbosa MA, Santos SG (2016) Circulating extracellular vesicles: their role in tissue repair and regeneration. Transfus Apheresis Sci 55:53–61. doi:10.1016/j.transci.2016.07.015

    Article  Google Scholar 

  25. Koniusz S, Andrzejewska A, Muraca M, Srivastava AK, Janowski M, Lukomska B (2016) Extracellular vesicles in physiology, pathology, and therapy of the immune and central nervous system, with focus on extracellular vesicles derived from mesenchymal stem cells as therapeutic tools. Front Cell Neurosci 10:109. doi:10.3389/fncel.2016.00109

    Article  PubMed  PubMed Central  Google Scholar 

  26. Robbins PD, Dorronsoro A, Booker CN (2016) Regulation of chronic inflammatory and immune processes by extracellular vesicles. J Clin Investig 126:1173–1180. doi:10.1172/JCI81131

    Article  PubMed  PubMed Central  Google Scholar 

  27. Merino-Gonzalez C, Zuniga FA, Escudero C, Ormazabal V, Reyes C, Nova-Lamperti E, Salomon C, Aguayo C (2016) Mesenchymal stem cell-derived extracellular vesicles promote angiogenesis: potencial clinical application. Front Physiol 7:24. doi:10.3389/fphys.2016.00024

    Article  PubMed  PubMed Central  Google Scholar 

  28. Kinoshita T, Yip KW, Spence T, Liu FF (2017) MicroRNAs in extracellular vesicles: potential cancer biomarkers. J Hum Genet 62:67–74. doi:10.1038/jhg.2016.87

    Article  CAS  PubMed  Google Scholar 

  29. Gillet V, Hunting DJ, Takser L (2016) Turing revisited: decoding the microRNA messages in brain extracellular vesicles for early detection of neurodevelopmental disorders. Curr Environ Health Rep 3:188–201. doi:10.1007/s40572-016-0093-0

    Article  PubMed  PubMed Central  Google Scholar 

  30. Vader P, Mol EA, Pasterkamp G, Schiffelers RM (2016) Extracellular vesicles for drug delivery. Adv Drug Deliv Rev 106:148–156. doi:10.1016/j.addr.2016.02.006

    Article  CAS  PubMed  Google Scholar 

  31. Anderson HC, Garimella R, Tague SE (2005) The role of matrix vesicles in growth plate development and biomineralization. Front Biosci: J Virtual Libr 10:822–837

    Article  CAS  Google Scholar 

  32. Nahar NN, Missana LR, Garimella R, Tague SE, Anderson HC (2008) Matrix vesicles are carriers of bone morphogenetic proteins (BMPs), vascular endothelial growth factor (VEGF), and noncollagenous matrix proteins. J Bone Miner Metab 26:514–519. doi:10.1007/s00774-008-0859-z

    Article  CAS  PubMed  Google Scholar 

  33. Proff P, Romer P (2009) The molecular mechanism behind bone remodelling: a review. Clin Oral Investig 13:355–362. doi:10.1007/s00784-009-0268-2

    Article  PubMed  Google Scholar 

  34. Ge M, Ke R, Cai T, Yang J, Mu X (2015) Identification and proteomic analysis of osteoblast-derived exosomes. Biochem Biophys Res Commun 467:27–32. doi:10.1016/j.bbrc.2015.09.135

    Article  CAS  PubMed  Google Scholar 

  35. Valenti MT, Dalle Carbonare L, Mottes M (2016) Hypophosphatasia and mesenchymal stem cells: a therapeutic promise. Int J Stem Cell Res Ther 3:1–3. doi:10.3390/ijms18010041

    Article  Google Scholar 

  36. Cui Y, Luan J, Li H, Zhou X, Han J (2016) Exosomes derived from mineralizing osteoblasts promote ST2 cell osteogenic differentiation by alteration of microRNA expression. FEBS Lett 590:185–192. doi:10.1002/1873-3468.12024

    Article  CAS  PubMed  Google Scholar 

  37. Morhayim J, van de Peppel J, Demmers JA, Kocer G, Nigg AL, van Driel M, Chiba H, van Leeuwen JP (2015) Proteomic signatures of extracellular vesicles secreted by nonmineralizing and mineralizing human osteoblasts and stimulation of tumor cell growth. FASEB J 29:274–285. doi:10.1096/fj.14-261404

    Article  CAS  PubMed  Google Scholar 

  38. Morhayim J, van de Peppel J, Braakman E, Rombouts EW, Ter Borg MN, Dudakovic A, Chiba H, van der Eerden BC, Raaijmakers MH, van Wijnen AJ, Cornelissen JJ, van Leeuwen JP (2016) Osteoblasts secrete miRNA-containing extracellular vesicles that enhance expansion of human umbilical cord blood cells. Sci Rep 6:32034. doi:10.1038/srep32034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Nair R, Santos L, Awasthi S, von Erlach T, Chow LW, Bertazzo S, Stevens MM (2014) Extracellular vesicles derived from preosteoblasts influence embryonic stem cell differentiation. Stem Cells Dev 23:1625–1635. doi:10.1089/scd.2013.0633

    Article  CAS  PubMed  Google Scholar 

  40. Burgess TL, Qian Y, Kaufman S, Ring BD, Van G, Capparelli C, Kelley M, Hsu H, Boyle WJ, Dunstan CR, Hu S, Lacey DL (1999) The ligand for osteoprotegerin (OPGL) directly activates mature osteoclasts. J Cell Biol 145:527–538

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Huynh N, VonMoss L, Smith D, Rahman I, Felemban MF, Zuo J, Rody WJ Jr, McHugh KP, Holliday LS (2016) Characterization of regulatory extracellular vesicles from osteoclasts. J Dent Res 95:673–679. doi:10.1177/0022034516633189

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Shapiro IM, Landis WJ, Risbud MV (2015) Matrix vesicles: are they anchored exosomes?. Bone 79:29–36. doi:10.1016/j.bone.2015.05.013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Kagiya T, Taira M (2013) Expression of microRNAs in the extracellular microvesicles of murine osteoclasts. J Oral Tissue Eng 10:142–150

    Google Scholar 

  44. Kagiya T, Nakamura S (2013) Expression profiling of microRNAs in RAW264.7 cells treated with a combination of tumor necrosis factor alpha and RANKL during osteoclast differentiation. J Periodontal Res 48:373–385. doi:10.1111/jre.12017

    Article  CAS  PubMed  Google Scholar 

  45. Lee DY, Deng Z, Wang CH, Yang BB (2007) MicroRNA-378 promotes cell survival, tumor growth, and angiogenesis by targeting SuFu and Fus-1 expression. Proc Natl Acad Sci USA 104:20350–20355. doi:10.1073/pnas.0706901104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Fasanaro P, Greco S, Lorenzi M, Pescatori M, Brioschi M, Kulshreshtha R, Banfi C, Stubbs A, Calin GA, Ivan M, Capogrossi MC, Martelli F (2009) An integrated approach for experimental target identification of hypoxia-induced miR-210. J Biol Chem 284:35134–35143. doi:10.1074/jbc.M109.052779

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Tsuchiya S, Fujiwara T, Sato F, Shimada Y, Tanaka E, Sakai Y, Shimizu K, Tsujimoto G (2011) MicroRNA-210 regulates cancer cell proliferation through targeting fibroblast growth factor receptor-like 1 (FGFRL1). J Biol Chem 286:420–428. doi:10.1074/jbc.M110.170852

    Article  CAS  PubMed  Google Scholar 

  48. Sugatani T, Hruska KA (2007) MicroRNA-223 is a key factor in osteoclast differentiation. J Cell Biochem 101:996–999. doi:10.1002/jcb.21335

    Article  CAS  PubMed  Google Scholar 

  49. Papaioannou G, Inloes JB, Nakamura Y, Paltrinieri E, Kobayashi T (2013) let-7 and miR-140 microRNAs coordinately regulate skeletal development. Proc Natl Acad Sci USA 110:E3291–E3300. doi:10.1073/pnas.1302797110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Shi K, Lu J, Zhao Y, Wang L, Li J, Qi B, Li H, Ma C (2013) MicroRNA-214 suppresses osteogenic differentiation of C2C12 myoblast cells by targeting Osterix. Bone 55:487–494. doi:10.1016/j.bone.2013.04.002

    Article  CAS  PubMed  Google Scholar 

  51. Wang X, Guo B, Li Q, Peng J, Yang Z et al (2013) miR-214 targets ATF4 to inhibit bone formation. Nat Med 19:93–100. doi:10.1038/nm.3026

    Article  PubMed  Google Scholar 

  52. Zhao C, Sun W, Zhang P, Ling S, Li Y, Zhao D, Peng J, Wang A, Li Q, Song J, Wang C, Xu X, Xu Z, Zhong G, Han B, Chang YZ (2015) miR-214 promotes osteoclastogenesis by targeting Pten/PI3k/Akt pathway. RNA Biol 12:343–353. doi:10.1080/15476286.2015.1017205

    Article  PubMed  PubMed Central  Google Scholar 

  53. Li D, Liu J, Guo B, Liang C, Dang L et al (2016) Osteoclast-derived exosomal miR-214-3p inhibits osteoblastic bone formation. Nat Commun 7:10872. doi:10.1038/ncomms10872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Sun W, Zhao C, Li Y, Wang L, Nie G et al (2016) Osteoclast-derived microRNA-containing exosomes selectively inhibit osteoblast activity. Cell Discov 2:16015. doi:10.1038/celldisc.2016.15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Zhang B, Yeo RW, Tan KH, Lim SK (2016) Focus on extracellular vesicles: therapeutic potential of stem cell-derived extracellular vesicles. Int J Mol Sci 17:174. doi:10.3390/ijms17020174

    Article  PubMed  PubMed Central  Google Scholar 

  56. Phinney DG, Prockop DJ (2007) Concise review: mesenchymal stem/multipotent stromal cells: the state of transdifferentiation and modes of tissue repair—current views. Stem Cells 25:2896–2902. doi:10.1634/stemcells.2007-0637

    Article  PubMed  Google Scholar 

  57. Ronne WYY, Ruenn CL, Kok HT, Sai KL (2013) Exosome: a novel and safer therapeutic refinement of mesenchymal stem cell. J Circ Biomark 1:1–12. doi:10.5772/57460

    Google Scholar 

  58. Thery C (2011) Exosomes: secreted vesicles and intercellular communications. F1000 Biol Rep 3:15. doi:10.3410/B3-15

    Article  PubMed  PubMed Central  Google Scholar 

  59. Baglio SR, Pegtel DM, Baldini N (2012) Mesenchymal stem cell secreted vesicles provide novel opportunities in (stem) cell-free therapy. Front Physiol 3:359. doi:10.3389/fphys.2012.00359

    Article  PubMed  PubMed Central  Google Scholar 

  60. Yeo RW, Lai RC, Zhang B, Tan SS, Yin Y, Teh BJ, Lim SK (2013) Mesenchymal stem cell: an efficient mass producer of exosomes for drug delivery. Adv Drug Deliv Rev 65:336–341. doi:10.1016/j.addr.2012.07.001

    Article  CAS  PubMed  Google Scholar 

  61. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147

    Article  CAS  PubMed  Google Scholar 

  62. Maumus M, Guerit D, Toupet K, Jorgensen C, Noel D (2011) Mesenchymal stem cell-based therapies in regenerative medicine: applications in rheumatology. Stem Cell Res Ther 2:14. doi:10.1186/scrt55

    Article  PubMed  PubMed Central  Google Scholar 

  63. Ranganath SH, Levy O, Inamdar MS, Karp JM (2012) Harnessing the mesenchymal stem cell secretome for the treatment of cardiovascular disease. Cell Stem Cell 10:244–258. doi:10.1016/j.stem.2012.02.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Martin PJ, Haren N, Ghali O, Clabaut A, Chauveau C, Hardouin P, Broux O (2015) Adipogenic RNAs are transferred in osteoblasts via bone marrow adipocytes-derived extracellular vesicles (EVs). BMC cell Biol 16:10. doi:10.1186/s12860-015-0057-5

    Article  PubMed  PubMed Central  Google Scholar 

  65. Zhao L, Jiang S, Hantash BM (2010) Transforming growth factor beta1 induces osteogenic differentiation of murine bone marrow stromal cells. Tissue Eng Part A 16:725–733. doi:10.1089/ten.TEA.2009.0495

    Article  CAS  PubMed  Google Scholar 

  66. Narayanan R, Huang CC, Ravindran S (2016) Hijacking the cellular mail: exosome mediated differentiation of mesenchymal stem cells. Stem Cells Int 2016:3808674. doi:10.1155/2016/3808674

    Article  PubMed  PubMed Central  Google Scholar 

  67. Collino F, Deregibus MC, Bruno S, Sterpone L, Aghemo G, Viltono L, Tetta C, Camussi G (2010) Microvesicles derived from adult human bone marrow and tissue specific mesenchymal stem cells shuttle selected pattern of miRNAs. PLoS One 5:e11803. doi:10.1371/journal.pone.0011803

    Article  PubMed  PubMed Central  Google Scholar 

  68. Baglio SR, Rooijers K, Koppers-Lalic D, Verweij FJ, Perez Lanzon M, Zini N, Naaijkens B, Perut F, Niessen HW, Baldini N, Pegtel DM (2015) Human bone marrow- and adipose-mesenchymal stem cells secrete exosomes enriched in distinctive miRNA and tRNA species. Stem Cell Res Ther 6:127. doi:10.1186/s13287-015-0116-z

    Article  PubMed  PubMed Central  Google Scholar 

  69. Kim HS, Choi DY, Yun SJ, Choi SM, Kang JW, Jung JW, Hwang D, Kim KP, Kim DW (2012) Proteomic analysis of microvesicles derived from human mesenchymal stem cells. J Proteome Res 11:839–849. doi:10.1021/pr200682z

    Article  CAS  PubMed  Google Scholar 

  70. Xu JF, Yang GH, Pan XH, Zhang SJ, Zhao C, Qiu BS, Gu HF, Hong JF, Cao L, Chen Y, Xia B, Bi Q, Wang YP (2014) Altered microRNA expression profile in exosomes during osteogenic differentiation of human bone marrow-derived mesenchymal stem cells. PLoS One 9:e114627. doi:10.1371/journal.pone.0114627

    Article  PubMed  PubMed Central  Google Scholar 

  71. Qin Y, Wang L, Gao Z, Chen G, Zhang C (2016) Bone marrow stromal/stem cell-derived extracellular vesicles regulate osteoblast activity and differentiation in vitro and promote bone regeneration in vivo. Sci Rep 6:21961. doi:10.1038/srep21961

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Mardones R, Jofre CM, Minguell JJ (2015) Cell therapy and tissue engineering approaches for cartilage repair and/or regeneration. Int J Stem Cells 8:48–53. doi:10.15283/ijsc.2015.8.1.48

    Article  PubMed  PubMed Central  Google Scholar 

  73. Tao SC, Yuan T, Zhang YL, Yin WJ, Guo SC, Zhang CQ (2017) Exosomes derived from miR-140-5p-overexpressing human synovial mesenchymal stem cells enhance cartilage tissue regeneration and prevent osteoarthritis of the knee in a rat model. Theranostics 7:180–195. doi:10.7150/thno.17133

    Article  PubMed  PubMed Central  Google Scholar 

  74. Liu S, Liu D, Chen C, Hamamura K, Moshaverinia A, Yang R, Liu Y, Jin Y, Shi S (2015) MSC transplantation improves osteopenia via epigenetic regulation of notch signaling in lupus. Cell Metab 22:606–618. doi:10.1016/j.cmet.2015.08.018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Martins M, Ribeiro D, Martins A, Reis RL, Neves NM (2016) Extracellular vesicles derived from osteogenically induced human bone marrow mesenchymal stem cells can modulate lineage commitment. Stem Cell Rep 6:284–291. doi:10.1016/j.stemcr.2016.01.001

    Article  CAS  Google Scholar 

  76. Wang KX, Xu LL, Rui YF, Huang S, Lin SE, Xiong JH, Li YH, Lee WY, Li G (2015) The effects of secretion factors from umbilical cord derived mesenchymal stem cells on osteogenic differentiation of mesenchymal stem cells. PLoS One 10:e0120593. doi:10.1371/journal.pone.0120593

    Article  PubMed  PubMed Central  Google Scholar 

  77. Omar OM, Graneli C, Ekstrom K, Karlsson C, Johansson A, Lausmaa J, Wexell CL, Thomsen P (2011) The stimulation of an osteogenic response by classical monocyte activation. Biomaterials 32:8190–8204. doi:10.1016/j.biomaterials.2011.07.055

    Article  CAS  PubMed  Google Scholar 

  78. Ekstrom K, Omar O, Graneli C, Wang X, Vazirisani F, Thomsen P (2013) Monocyte exosomes stimulate the osteogenic gene expression of mesenchymal stem cells. PLoS One 8:e75227. doi:10.1371/journal.pone.0075227

    Article  PubMed  PubMed Central  Google Scholar 

  79. Wang Z, Ding L, Zheng XL, Wang HX, Yan HM (2014) [DC-derived exosomes induce osteogenic differentiation of mesenchymal stem cells] (in Chinese). Zhongguo shi yan xue ye xue za zhi 22:600–604. doi:10.7534/j.issn.1009-2137.2014.03.005

    PubMed  Google Scholar 

  80. Raimondi L, De Luca A, Amodio N, Manno M, Raccosta S, Taverna S, Bellavia D, Naselli F, Fontana S, Schillaci O, Giardino R, Fini M, Tassone P, Santoro A, De Leo G, Giavaresi G, Alessandro R (2015) Involvement of multiple myeloma cell-derived exosomes in osteoclast differentiation. Oncotarget 6:13772–13789. doi:10.18632/oncotarget.3830

    Article  PubMed  PubMed Central  Google Scholar 

  81. Anderson HC, Mulhall D, Garimella R (2010) Role of extracellular membrane vesicles in the pathogenesis of various diseases, including cancer, renal diseases, atherosclerosis, and arthritis. Lab Investig J Tech Methods Pathol 90:1549–1557. doi:10.1038/labinvest.2010.152

    Article  CAS  Google Scholar 

  82. Ali SY, Griffiths S (1983) Formation of calcium phosphate crystals in normal and osteoarthritic cartilage. Ann Rheum Dis 42:45–48

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Kato T, Miyaki S, Ishitobi H, Nakamura Y, Nakasa T, Lotz MK, Ochi M (2014) Exosomes from IL-1beta stimulated synovial fibroblasts induce osteoarthritic changes in articular chondrocytes. Arthritis Res Ther 16:R163. doi:10.1186/ar4679

    Article  PubMed  PubMed Central  Google Scholar 

  84. Karlsson T, Lundholm M, Widmark A, Persson E (2016) Tumor cell-derived exosomes from the prostate cancer cell line TRAMP-C1 impair osteoclast formation and differentiation. PLoS One 11:e0166284. doi:10.1371/journal.pone.0166284

    Article  PubMed  PubMed Central  Google Scholar 

  85. Inder KL, Ruelcke JE, Petelin L, Moon H, Choi E, Rae J, Blumenthal A, Hutmacher D, Saunders NA, Stow JL, Parton RG, Hill MM (2014) Cavin-1/PTRF alters prostate cancer cell-derived extracellular vesicle content and internalization to attenuate extracellular vesicle-mediated osteoclastogenesis and osteoblast proliferation. J Extracell Vesicles 3:23784. doi:10.3402/jev.v3.23784

    Article  Google Scholar 

  86. Garimella R, Washington L, Isaacson J, Vallejo J, Spence M, Tawfik O, Rowe P, Brotto M, Perez R (2014) Extracellular membrane vesicles derived from 143B osteosarcoma cells contain pro-osteoclastogenic cargo: a novel communication mechanism in osteosarcoma bone microenvironment. Transl Oncol 7:331–340. doi:10.1016/j.tranon.2014.04.011

    Article  PubMed  PubMed Central  Google Scholar 

  87. Oliveira MC, Di Ceglie I, Arntz OJ, van den Berg WB, van den Hoogen FH, Ferreira AV, van Lent PL, van de Loo FA (2017) Milk-derived nanoparticle fraction promotes the formation of small osteoclasts but reduces bone resorption. J Cell Physiol 232:225–233. doi:10.1002/jcp.25414

    Article  CAS  PubMed  Google Scholar 

  88. Oliveira MC, Arntz OJ, Blaney Davidson EN, van Lent PL, Koenders MI, van der Kraan PM, van den Berg WB, Ferreira AV, van de Loo FA (2016) Milk extracellular vesicles accelerate osteoblastogenesis but impair bone matrix formation. J Nutr Biochem 30:74–84. doi:10.1016/j.jnutbio.2015.11.017

    Article  CAS  PubMed  Google Scholar 

  89. Scita G, Di Fiore PP (2010) The endocytic matrix. Nature 463:464–473. doi:10.1038/nature08910

    Article  CAS  PubMed  Google Scholar 

  90. Ludwig AK, Giebel B (2012) Exosomes: small vesicles participating in intercellular communication. Int J Biochem Cell Biol 44:11–15. doi:10.1016/j.biocel.2011.10.005

    Article  CAS  PubMed  Google Scholar 

  91. Fang Y, Wu N, Gan X, Yan W, Morrell JC, Gould SJ (2007) Higher-order oligomerization targets plasma membrane proteins and HIV gag to exosomes. PLoS Biol 5:e158. doi:10.1371/journal.pbio.0050158

    Article  PubMed  PubMed Central  Google Scholar 

  92. Trajkovic K, Hsu C, Chiantia S, Rajendran L, Wenzel D, Wieland F, Schwille P, Brugger B, Simons M (2008) Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science 319:1244–1247. doi:10.1126/science.1153124

    Article  CAS  PubMed  Google Scholar 

  93. Raiborg C, Rusten TE, Stenmark H (2003) Protein sorting into multivesicular endosomes. Curr Opin Cell Biol 15:446–455

    Article  CAS  PubMed  Google Scholar 

  94. Franzen CA, Simms PE, Van Huis AF, Foreman KE, Kuo PC, Gupta GN (2014) Characterization of uptake and internalization of exosomes by bladder cancer cells. Biomed Res Int 2014:619829. doi:10.1155/2014/619829

    Article  PubMed  PubMed Central  Google Scholar 

  95. Mause SF, Weber C (2010) Microparticles: protagonists of a novel communication network for intercellular information exchange. Circ Res 107:1047–1057. doi:10.1161/CIRCRESAHA.110.226456

    Article  CAS  PubMed  Google Scholar 

  96. Schorey JS, Bhatnagar S (2008) Exosome function: from tumor immunology to pathogen biology. Traffic 9:871–881. doi:10.1111/j.1600-0854.2008.00734.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Oltra E (2014) Relevance of splicing on tumor-released exosome landscape: implications in cancer therapeutics. Front Endocrinol 5:194. doi:10.3389/fendo.2014.00194

    Article  Google Scholar 

  98. van der Pol E, Hoekstra AG, Sturk A, Otto C, van Leeuwen TG, Nieuwland R (2010) Optical and non-optical methods for detection and characterization of microparticles and exosomes. J Thromb Haemost 8:2596–2607. doi:10.1111/j.1538-7836.2010.04074.x

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We gratefully acknowledge financial support from the National Natural Science Foundation of China (NSFC; Grant No. 81502465).

Author information

Authors and Affiliations

  1. Key Laboratory for Space Bioscience and Space Biotechnology, School of Life Sciences, Northwestern Polytechnical University, 127 YouyiXilu, Xi’an, 710072, Shaanxi, People’s Republic of China

    Qi Li, Qiu-Ping Huang, Yi-Lin Wang & Qing-Sheng Huang

Authors
  1. Qi Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qiu-Ping Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yi-Lin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qing-Sheng Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Qi Li.

Ethics declarations

Conflict of interest

The authors declare that there are no conflict of interest.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, Q., Huang, QP., Wang, YL. et al. Extracellular vesicle-mediated bone metabolism in the bone microenvironment. J Bone Miner Metab 36, 1–11 (2018). https://doi.org/10.1007/s00774-017-0860-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00774-017-0860-5

Keywords

Search

Navigation