ATP and UTP stimulate bone morphogenetic protein-2,-4 and -5 gene expression and mineralization by rat primary osteoblasts involving PI3K/AKT pathway
The modulation of purinergic receptors plays an important role in the regulation of bone formation by the osteoblast. On the other hand, bone morphogenetic proteins (BMPs), members of the transforming growth factor-β superfamily, regulate the differentiation of osteoprogenitor bone cells and stimula...
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00144827_v319_n13_p2028_AyalaPena http://hdl.handle.net/20.500.12110/paper_00144827_v319_n13_p2028_AyalaPena |
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paper:paper_00144827_v319_n13_p2028_AyalaPena2023-06-08T14:37:18Z ATP and UTP stimulate bone morphogenetic protein-2,-4 and -5 gene expression and mineralization by rat primary osteoblasts involving PI3K/AKT pathway Scolaro, Luis Alberto ATP BMPs Osteoblast PI3K/AKT Purinergic receptor UTP 2 morpholino 8 phenylchromone adenosine diphosphate adenosine triphosphate alkaline phosphatase bone morphogenetic protein bone morphogenetic protein 2 bone morphogenetic protein 4 bone morphogenetic protein 5 calcium messenger RNA phosphatidylinositol 3 kinase protein kinase B purinergic receptor uridine diphosphate uridine triphosphate animal cell article bone cell bone development bone mineralization cell differentiation cell lysate cell proliferation cell structure controlled study enzyme activity newborn nonhuman ossification osteoblast osteolysis priority journal protein expression rat signal transduction Rattus The modulation of purinergic receptors plays an important role in the regulation of bone formation by the osteoblast. On the other hand, bone morphogenetic 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 their relation with the gene expression of osteogenic proteins BMP-2, BMP-4 and BMP-5 as well as of differentiation markers alkaline phosphatase (ALP) and bone sialoprotein (BSP). Our results indicate that 100μM ATP, ATPγS and UTP, but not ADP, ADPβS or UDP, 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 osteoblasts in the presence of 100μM 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-5 and BSP. 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. © 2013 Elsevier Inc. Fil:Scolaro, L.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2013 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00144827_v319_n13_p2028_AyalaPena http://hdl.handle.net/20.500.12110/paper_00144827_v319_n13_p2028_AyalaPena |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
ATP BMPs Osteoblast PI3K/AKT Purinergic receptor UTP 2 morpholino 8 phenylchromone adenosine diphosphate adenosine triphosphate alkaline phosphatase bone morphogenetic protein bone morphogenetic protein 2 bone morphogenetic protein 4 bone morphogenetic protein 5 calcium messenger RNA phosphatidylinositol 3 kinase protein kinase B purinergic receptor uridine diphosphate uridine triphosphate animal cell article bone cell bone development bone mineralization cell differentiation cell lysate cell proliferation cell structure controlled study enzyme activity newborn nonhuman ossification osteoblast osteolysis priority journal protein expression rat signal transduction Rattus |
| spellingShingle |
ATP BMPs Osteoblast PI3K/AKT Purinergic receptor UTP 2 morpholino 8 phenylchromone adenosine diphosphate adenosine triphosphate alkaline phosphatase bone morphogenetic protein bone morphogenetic protein 2 bone morphogenetic protein 4 bone morphogenetic protein 5 calcium messenger RNA phosphatidylinositol 3 kinase protein kinase B purinergic receptor uridine diphosphate uridine triphosphate animal cell article bone cell bone development bone mineralization cell differentiation cell lysate cell proliferation cell structure controlled study enzyme activity newborn nonhuman ossification osteoblast osteolysis priority journal protein expression rat signal transduction Rattus Scolaro, Luis Alberto ATP and UTP stimulate bone morphogenetic protein-2,-4 and -5 gene expression and mineralization by rat primary osteoblasts involving PI3K/AKT pathway |
| topic_facet |
ATP BMPs Osteoblast PI3K/AKT Purinergic receptor UTP 2 morpholino 8 phenylchromone adenosine diphosphate adenosine triphosphate alkaline phosphatase bone morphogenetic protein bone morphogenetic protein 2 bone morphogenetic protein 4 bone morphogenetic protein 5 calcium messenger RNA phosphatidylinositol 3 kinase protein kinase B purinergic receptor uridine diphosphate uridine triphosphate animal cell article bone cell bone development bone mineralization cell differentiation cell lysate cell proliferation cell structure controlled study enzyme activity newborn nonhuman ossification osteoblast osteolysis priority journal protein expression rat signal transduction Rattus |
| description |
The modulation of purinergic receptors plays an important role in the regulation of bone formation by the osteoblast. On the other hand, bone morphogenetic 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 their relation with the gene expression of osteogenic proteins BMP-2, BMP-4 and BMP-5 as well as of differentiation markers alkaline phosphatase (ALP) and bone sialoprotein (BSP). Our results indicate that 100μM ATP, ATPγS and UTP, but not ADP, ADPβS or UDP, 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 osteoblasts in the presence of 100μM 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-5 and BSP. 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. © 2013 Elsevier Inc. |
| author |
Scolaro, Luis Alberto |
| author_facet |
Scolaro, Luis Alberto |
| author_sort |
Scolaro, Luis Alberto |
| title |
ATP and UTP stimulate bone morphogenetic protein-2,-4 and -5 gene expression and mineralization by rat primary osteoblasts involving PI3K/AKT pathway |
| title_short |
ATP and UTP stimulate bone morphogenetic protein-2,-4 and -5 gene expression and mineralization by rat primary osteoblasts involving PI3K/AKT pathway |
| title_full |
ATP and UTP stimulate bone morphogenetic protein-2,-4 and -5 gene expression and mineralization by rat primary osteoblasts involving PI3K/AKT pathway |
| title_fullStr |
ATP and UTP stimulate bone morphogenetic protein-2,-4 and -5 gene expression and mineralization by rat primary osteoblasts involving PI3K/AKT pathway |
| title_full_unstemmed |
ATP and UTP stimulate bone morphogenetic protein-2,-4 and -5 gene expression and mineralization by rat primary osteoblasts involving PI3K/AKT pathway |
| title_sort |
atp and utp stimulate bone morphogenetic protein-2,-4 and -5 gene expression and mineralization by rat primary osteoblasts involving pi3k/akt pathway |
| publishDate |
2013 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00144827_v319_n13_p2028_AyalaPena http://hdl.handle.net/20.500.12110/paper_00144827_v319_n13_p2028_AyalaPena |
| work_keys_str_mv |
AT scolaroluisalberto atpandutpstimulatebonemorphogeneticprotein24and5geneexpressionandmineralizationbyratprimaryosteoblastsinvolvingpi3kaktpathway |
| _version_ |
1768543828981055488 |