Role of ecto-NTPDases on UDP-sensitive P2Y6 receptor activation during osteogenic differentiation of primary bone marrow stromal cells from postmenopausal women

• Type: Article in International Scientific Journal
• Date: 2012

Authors

Noronha Matos, JB (Author) Other; Costa, MA (Author) ICBAS; Magalhaes Cardoso, MT (Author) Other; Fátima Ferreirinha (Author) ICBAS; Pelletier, J (Author) Other; Freitas, R (Author) Other; Neves, JM (Author) Other; Sevigny, J (Author) Other; Paulo Correia de Sá (Author) ICBAS

Journal

Title: Journal of Cellular Physiology

Vol. 227

Pages: 2694-2709

ISSN: 0021-9541

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 27 Citations

Scopus - 25 Citations

Other information

Authenticus ID: P-002-9WS

DOI: 10.1002/jcp.23014

Abstract (EN): This study aimed at investigating the expression and function of uracil nucleotide-sensitive receptors (P2Y2, P2Y4, and P2Y6) on osteogenic differentiation of human bone marrow stromal cells (BMSCs) in culture. Bone marrow specimens were obtained from postmenopausal female patients (68 +/- 5 years old, n?=?18) undergoing total hip arthroplasty. UTP and UDP (100?mu M) facilitated osteogenic differentiation of the cells measured as increases in alkaline phosphatase (ALP) activity, without affecting cell proliferation. Uracil nucleotides concentration-dependently increased [Ca2+]i in BMSCs; their effects became less evident with time (7?>?21 days) of the cells in culture. Selective activation of P2Y6 receptors with the stable UDP analog, PSB 0474, mimicked the effects of both UTP and UDP, whereas UTP?S was devoid of effect. Selective blockade of P2Y6 receptors with MRS 2578 prevented [Ca2+]i rises and osteogenic differentiation caused by UDP at all culture time points. BMSCs are immunoreactive against P2Y2, P2Y4, and P2Y6 receptors. While the expression of P2Y6 receptors remained fairly constant (7 similar to 21 days), P2Y2 and P2Y4 became evident only in less proliferative and more differentiated cultures (7?<?21 days). The rate of extracellular UTP and UDP inactivation was higher in less proliferative and more differentiated cell populations. Immunoreactivity against NTPDase1, -2, and -3 rises as cells differentiate (7?<?21 days). Data show that uracil nucleotides are important regulators of osteogenic cells differentiation predominantly through the activation of UDP-sensitive P2Y6 receptors coupled to increases in [Ca2+]i. Endogenous actions of uracil nucleotides may be balanced through specific NTPDases determining whether osteoblast progenitors are driven into proliferation or differentiation. J. Cell. Physiol. 227: 26942709, 2012. (c) 2011 Wiley Periodicals, Inc.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 16