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Article
Membrane vesicles nucleate mineralo-organic nanoparticles and induce carbonate apatite precipitation in human body fluids
Journal of Biological Chemistry
  • Cheng-Yeu Wu, Chang Gung University
  • Jan Martel, Chang Gung University
  • Wei-Yun Cheng, Chang Gung University
  • Chao-Chih He, Chang Gung University
  • David M. Ojcius, Chang Gung University
  • John Ding-E. Young, Chang Gung University
ORCiD
David M. Ojcius: 0000-0003-1461-4495
Document Type
Article
DOI
10.1074/jbc.M113.492157
Publication Date
10-18-2013
Abstract
Recent studies indicate that membrane vesicles (MVs) secreted by various cells are associated with human diseases, including arthritis, atherosclerosis, cancer, and chronic kidney disease. The possibility that MVs may induce the formation of mineralo-organic nanoparticles (NPs) and ectopic calcification has not been investigated so far. Here, we isolated MVs ranging in size between 20 and 400 nm from human serum and FBS using ultracentrifugation and sucrose gradient centrifugation. The MV preparations consisted of phospholipid-bound vesicles containing the serum proteins albumin, fetuin-A, and apolipoprotein A1; the mineralization-associated enzyme alkaline phosphatase; and the exosome proteins TNFR1 and CD63. Notably, we observed that MVs induced mineral precipitation following inoculation and incubation in cell culture medium. The mineral precipitates consisted of round, mineralo-organic NPs containing carbonate hydroxyapatite, similar to previous descriptions of the so-called nanobacteria. Annexin V-immunogold staining revealed that the calcium-binding lipid phosphatidylserine (PS) was exposed on the external surface of serum MVs. Treatment of MVs with an anti-PS antibody significantly decreased their mineral seeding activity, suggesting that PS may provide nucleating sites for calcium phosphate deposition on the vesicles. These results indicate that MVs may represent nucleating agents that induce the formation of mineral NPs in body fluids. Given that mineralo-organic NPs represent precursors of calcification in vivo, our results suggest that MVs may initiate ectopic calcification in the human body.
Citation Information
Cheng-Yeu Wu, Jan Martel, Wei-Yun Cheng, Chao-Chih He, et al.. "Membrane vesicles nucleate mineralo-organic nanoparticles and induce carbonate apatite precipitation in human body fluids" Journal of Biological Chemistry Vol. 288 Iss. 42 (2013) p. 30571 - 30584 ISSN: 0021-9258
Available at: http://works.bepress.com/david-ojcius/156/