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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • January 21, 2014

Published In

Volume / Issue

  • 111 / 3

Start / End Page

  • 990 - 995

PubMed ID

  • 24395775

Pubmed Central ID

  • PMC3903237

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Digital Object Identifier (DOI)

  • 10.1073/pnas.1321717111


  • eng

Conference Location

  • United States