ATP and UTP stimulate bone morphogenetic protein-2,-4 and -5 gene expression and mineralization by rat primary osteoblasts involving PI3K/AKT pathway.

AYALA PEÑA, VICTORIA; SCOLARO, LUIS; SANTILLÁN, GRACIELA

EXPERIMENTAL CELL RESEARCH

ELSEVIER INC

Lugar: Amsterdam ; Año: 2013 vol. 319 p. 2028 - 2036

0014-4827

The modulation of purinergic receptors plays an important role in the regulation of bone formation the osteoblast.On the other hand,bonemorphogenetic proteins(BMPs),members of the transforming growth factor-β superfamily,regulate the differentiation of osteoprogenitor bone cells and stimulate bone formation.In this study,we investigate the effects of several nucleotides on osteoblast differentiation and function,and the irrelation with the gene expression of osteogenic proteins BMP-2,BMP-4 and BMP-5 as well as of differentiation markers alkaline phosphatase(ALP)and bonesialoprotein(BSP).Our results indicate that 100 μM ATP, ATPγS andUTP,butnotADP,ADPβS orUDP,promote ALP activity in rat primary osteoblasts, showing a peak about day 7 of the treatment.ATP,ATPγS and UTP also increase the mRNA levels of ALP,BMP-2,BMP-4,BMP-5 and BSP.Both the ALP activity and ALP and BMP-4 mRNA increments induced by ATP and UTP are inhibited by Ly294002, a PI3K inhibitor, suggesting the involvement of PI3K/AKT signaling pathway in purinergic modulation of osteoblast differentiation. Furthermore,bone mineralization enhance 1 and 1.5 fold after culturing osteoblast sinthe presence of 100 μM ATP or UTP,respectively, but not of ADP or UDP for 22 days .This information suggests that P2Y2 receptors(responsive to ATP, ATPγS and UTP)enhance osteoblast differentiation involving PI3K/AKT signaling pathway activation and gene expression induction of ALP,BMP-2, BMP-4,BMP-5andBSP.Our findings state a novel molecular mechanism that involves specific gene expression activation of osteoblast function by the purinoreceptors,which would be of help in setting up new pharmacological strategies for the intervention in bone loss pathologies.