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

Yu Ru V. Shih, Yongsung Hwang, Ameya Phadke, Heemin Kang, Nathaniel S. Hwang, Eduardo J. Caro, Steven Nguyen, Michael Siu, Emmanuel A. Theodorakis, Nathan C. Gianneschi, Kenneth S. Vecchio, Shu Chien, Oscar K. Lee, Shyni Varghese

Research output: Contribution to journalArticle

157 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)990-995
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number3
DOIs
Publication statusPublished - 2014 Jan 21
Externally publishedYes

Fingerprint

Adenosine
Stem Cells
Phosphates
Bone and Bones
Adenosine Triphosphate
Biocompatible Materials
Mesenchymal Stromal Cells
Osteogenesis
Type III Sodium-Phosphate Cotransporter Proteins
Autocrine Communication
Paracrine Communication
Bone Regeneration
Purinergic P1 Receptors
Metabolic Bone Diseases
Minerals
Homeostasis
Ions
calcium phosphate

Keywords

  • Biomimetic material
  • Bone metabolism
  • Mineralized matrix
  • Phosphate signaling

ASJC Scopus subject areas

  • General

Cite this

Calcium phosphate-bearing matrices induce osteogenic differentiation of stem cells through adenosine signaling. / Shih, Yu Ru V.; Hwang, Yongsung; Phadke, Ameya; Kang, Heemin; Hwang, Nathaniel S.; Caro, Eduardo J.; Nguyen, Steven; Siu, Michael; Theodorakis, Emmanuel A.; Gianneschi, Nathan C.; Vecchio, Kenneth S.; Chien, Shu; Lee, Oscar K.; Varghese, Shyni.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, No. 3, 21.01.2014, p. 990-995.

Research output: Contribution to journalArticle

Shih, YRV, 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 2014, 'Calcium phosphate-bearing matrices induce osteogenic differentiation of stem cells through adenosine signaling', Proceedings of the National Academy of Sciences of the United States of America, vol. 111, no. 3, pp. 990-995. https://doi.org/10.1073/pnas.1321717111
Shih, Yu Ru V. ; Hwang, Yongsung ; Phadke, Ameya ; Kang, Heemin ; Hwang, Nathaniel S. ; Caro, Eduardo J. ; Nguyen, Steven ; Siu, Michael ; Theodorakis, Emmanuel A. ; Gianneschi, Nathan C. ; Vecchio, Kenneth S. ; Chien, Shu ; Lee, Oscar K. ; Varghese, Shyni. / Calcium phosphate-bearing matrices induce osteogenic differentiation of stem cells through adenosine signaling. In: Proceedings of the National Academy of Sciences of the United States of America. 2014 ; Vol. 111, No. 3. pp. 990-995.
@article{1be78f6107354d11adce30cc772b263b,
title = "Calcium phosphate-bearing matrices induce osteogenic differentiation of stem cells through adenosine signaling",
abstract = "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.",
keywords = "Biomimetic material, Bone metabolism, Mineralized matrix, Phosphate signaling",
author = "Shih, {Yu Ru V.} and Yongsung Hwang and Ameya Phadke and Heemin Kang and Hwang, {Nathaniel S.} and Caro, {Eduardo J.} and Steven Nguyen and Michael Siu and Theodorakis, {Emmanuel A.} and Gianneschi, {Nathan C.} and Vecchio, {Kenneth S.} and Shu Chien and Lee, {Oscar K.} and Shyni Varghese",
year = "2014",
month = "1",
day = "21",
doi = "10.1073/pnas.1321717111",
language = "English",
volume = "111",
pages = "990--995",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "3",

}

TY - JOUR

T1 - Calcium phosphate-bearing matrices induce osteogenic differentiation of stem cells through adenosine signaling

AU - Shih, Yu Ru V.

AU - Hwang, Yongsung

AU - Phadke, Ameya

AU - Kang, Heemin

AU - Hwang, Nathaniel S.

AU - Caro, Eduardo J.

AU - Nguyen, Steven

AU - Siu, Michael

AU - Theodorakis, Emmanuel A.

AU - Gianneschi, Nathan C.

AU - Vecchio, Kenneth S.

AU - Chien, Shu

AU - Lee, Oscar K.

AU - Varghese, Shyni

PY - 2014/1/21

Y1 - 2014/1/21

N2 - 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.

AB - 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.

KW - Biomimetic material

KW - Bone metabolism

KW - Mineralized matrix

KW - Phosphate signaling

UR - http://www.scopus.com/inward/record.url?scp=84892925815&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84892925815&partnerID=8YFLogxK

U2 - 10.1073/pnas.1321717111

DO - 10.1073/pnas.1321717111

M3 - Article

C2 - 24395775

AN - SCOPUS:84892925815

VL - 111

SP - 990

EP - 995

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 3

ER -