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Calcium phosphate-bearing matrices induce osteogenic differentiation of stem cells through adenosine signaling.

Publication ,  Journal Article
Shih, Y-RV; Hwang, Y; Phadke, A; Kang, H; Hwang, NS; Caro, EJ; Nguyen, S; Siu, M; Theodorakis, EA; Gianneschi, NC; Vecchio, KS; Chien, S ...
Published in: Proc Natl Acad Sci U S A
January 21, 2014

Synthetic matrices emulating the physicochemical properties of tissue-specific ECMs are being developed at a rapid pace to regulate stem cell fate. Biomaterials containing calcium phosphate (CaP) moieties have been shown to support osteogenic differentiation of stem and progenitor cells and bone tissue formation. By using a mineralized synthetic matrix mimicking a CaP-rich bone microenvironment, we examine a molecular mechanism through which CaP minerals induce osteogenesis of human mesenchymal stem cells with an emphasis on phosphate metabolism. Our studies show that extracellular phosphate uptake through solute carrier family 20 (phosphate transporter), member 1 (SLC20a1) supports osteogenic differentiation of human mesenchymal stem cells via adenosine, an ATP metabolite, which acts as an autocrine/paracrine signaling molecule through A2b adenosine receptor. Perturbation of SLC20a1 abrogates osteogenic differentiation by decreasing intramitochondrial phosphate and ATP synthesis. Collectively, this study offers the demonstration of a previously unknown mechanism for the beneficial role of CaP biomaterials in bone repair and the role of phosphate ions in bone physiology and regeneration. These findings also begin to shed light on the role of ATP metabolism in bone homeostasis, which may be exploited to treat bone metabolic diseases.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

January 21, 2014

Volume

111

Issue

3

Start / End Page

990 / 995

Location

United States

Related Subject Headings

  • Stem Cells
  • Sodium-Phosphate Cotransporter Proteins, Type III
  • Signal Transduction
  • Regeneration
  • Receptor, Adenosine A2B
  • RNA, Small Interfering
  • Phosphates
  • Phenotype
  • Osteogenesis
  • Mesenchymal Stem Cells
 

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Shih, Y.-R., Hwang, Y., Phadke, A., Kang, H., Hwang, N. S., Caro, E. J., … Varghese, S. (2014). Calcium phosphate-bearing matrices induce osteogenic differentiation of stem cells through adenosine signaling. Proc Natl Acad Sci U S A, 111(3), 990–995. https://doi.org/10.1073/pnas.1321717111
Shih, Yu-Ru V., YongSung Hwang, Ameya Phadke, Heemin Kang, Nathaniel S. Hwang, Eduardo J. Caro, Steven Nguyen, et al. “Calcium phosphate-bearing matrices induce osteogenic differentiation of stem cells through adenosine signaling.Proc Natl Acad Sci U S A 111, no. 3 (January 21, 2014): 990–95. https://doi.org/10.1073/pnas.1321717111.
Shih Y-RV, Hwang Y, Phadke A, Kang H, Hwang NS, Caro EJ, et al. Calcium phosphate-bearing matrices induce osteogenic differentiation of stem cells through adenosine signaling. Proc Natl Acad Sci U S A. 2014 Jan 21;111(3):990–5.
Shih, Yu-Ru V., et al. “Calcium phosphate-bearing matrices induce osteogenic differentiation of stem cells through adenosine signaling.Proc Natl Acad Sci U S A, vol. 111, no. 3, Jan. 2014, pp. 990–95. Pubmed, doi:10.1073/pnas.1321717111.
Shih Y-RV, Hwang Y, Phadke A, Kang H, Hwang NS, Caro EJ, Nguyen S, Siu M, Theodorakis EA, Gianneschi NC, Vecchio KS, Chien S, Lee OK, Varghese S. Calcium phosphate-bearing matrices induce osteogenic differentiation of stem cells through adenosine signaling. Proc Natl Acad Sci U S A. 2014 Jan 21;111(3):990–995.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

January 21, 2014

Volume

111

Issue

3

Start / End Page

990 / 995

Location

United States

Related Subject Headings

  • Stem Cells
  • Sodium-Phosphate Cotransporter Proteins, Type III
  • Signal Transduction
  • Regeneration
  • Receptor, Adenosine A2B
  • RNA, Small Interfering
  • Phosphates
  • Phenotype
  • Osteogenesis
  • Mesenchymal Stem Cells