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Biomineralized matrices promote osteogenic differentiation of human mesenchymal stem cells: A mechanistic study
Author(s) -
Shih Yuru Ver,
Phadke Ameya,
Siu Michael,
Lee Oscar K.S.,
Chien Shu,
Varghese Shyni
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb65
Subject(s) - mesenchymal stem cell , microbiology and biotechnology , paracrine signalling , chemistry , autocrine signalling , extracellular matrix , gene knockdown , runx2 , intracellular , matrix (chemical analysis) , biochemistry , alkaline phosphatase , biology , enzyme , apoptosis , receptor , chromatography
Human mesenchymal stem cells (hMSCs) are ideal cells for skeletal tissue engineering due to their expandability and ability to undergo osteogenic differentiation. Recently, we have shown that hMSCs cultured on biomineralized matrices undergo osteogenic differentiation in the absence of any osteogenic inducing soluble factors. This finding in conjunction with the occurrence of dynamic dissolution of the calcium‐phosphate phase of the matrix suggest that inorganic ions such as Pi play a direct functional role in directing osteogenic differentiation of hMSCs on mineralized matrices. hMSCs cultured on biomineralized matrices upregulated Runx2, while knockdown of the transmembrane phosphate transporter SLC20a1 abrogated such an increase, similar to that observed on culture in high Pi (5 mM; PM). These findings exemplify the role of Pi, which enters the cells through SLC20a1, in promoting osteogenesis of hMSCs. Furthermore, the intracellular and intra‐mitochondrial phosphate, as well as intracellular ATP content, were elevated during PM culture, but decreased after SLC20a1 knockdown. Our results demonstrate a previously unknown mechanism of the osteoinductivity of mineralized matrices involving inorganic ions where they serve as a substrate for ATP synthesis and possibly acting as an extracellular autocrine/paracrine signaling molecule. (NSC 99‐2911‐I‐009‐101; NSC 99‐2911‐I‐010‐501).