Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2002-1-28
pubmed:abstractText
The cyclic monophosphate nucleotides (cyclic adenosine monophosphate [cAMP] and cyclic guanosine monophosphate [cGMP]) are found ubiquitously in mammalian cells and act as second messenger transducers to effect the intracellular actions of a variety of hormones, cytokines, and neurotransmitters. In turn, these nucleotides also modulate the signal transduction processes regulated by a range of cytokines and growth factors. Previously, we have reported that pentoxifylline, a nonselective phosphodiesterase (PDE) inhibitor, can promote osteoblastic differentiation by elevating intracellular cAMP levels and, consequently, enhance bone formation in vivo and in vitro. In this study, reverse-transcription polymerase chain reaction (RT-PCR) analysis of the osteoblastic cell lines, MC3T3-E1 and ST2 revealed the presence of PDE1, PDE2, PDE3, PDE4, PDE7, PDE8, and PDE9. We examined the effect of selective inhibitors for a respective PDE isozyme on the capacity of bone morphogenetic protein 4 (BMP-4)-induced alkaline phosphatase (ALP) activity, a cellular differentiation marker, in cells with osteogenetic potential. The results indicate that selective inhibitors for PDE2, PDE3, and PDE4 enhanced the BMP-4-induced ALP activity in a dose-dependent manner in ST2 cells but not in MC3T3-E1 cells. Northern blot analysis also revealed that the selective inhibitors for PDE2, PDE3, and PDE4 enhanced the levels of expression of messenger RNAs (mRNAs) of ALP, osteopontin (OP), and collagen type I in ST2 cells but not in MC3T3-E1 cells except for the treatment with PDE4 inhibitor. Given these data, we conclude that PDE isozymes are involved in the modulation of osteoblastic differentiation mainly at an early stage. Additionally, selective inhibitors for PDE2, PDE3, and PDE4 appear to promote the differentiation of osteogenic precursor cells toward an osteoblastic phenotype.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Alkaline Phosphatase, http://linkedlifedata.com/resource/pubmed/chemical/Bmp4 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Protein 4, http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes, http://linkedlifedata.com/resource/pubmed/chemical/Milrinone, http://linkedlifedata.com/resource/pubmed/chemical/Osteopontin, http://linkedlifedata.com/resource/pubmed/chemical/Phosphodiesterase Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Phosphoric Diester Hydrolases, http://linkedlifedata.com/resource/pubmed/chemical/Rolipram, http://linkedlifedata.com/resource/pubmed/chemical/Sialoglycoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Spp1 protein, mouse
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0884-0431
pubmed:author
pubmed:issnType
Print
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
249-56
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11811555-Alkaline Phosphatase, pubmed-meshheading:11811555-Animals, pubmed-meshheading:11811555-Bone Morphogenetic Protein 4, pubmed-meshheading:11811555-Bone Morphogenetic Proteins, pubmed-meshheading:11811555-Cell Differentiation, pubmed-meshheading:11811555-Cells, Cultured, pubmed-meshheading:11811555-Gene Expression Regulation, pubmed-meshheading:11811555-Isoenzymes, pubmed-meshheading:11811555-Mice, pubmed-meshheading:11811555-Milrinone, pubmed-meshheading:11811555-Osteoblasts, pubmed-meshheading:11811555-Osteopontin, pubmed-meshheading:11811555-Phosphodiesterase Inhibitors, pubmed-meshheading:11811555-Phosphoric Diester Hydrolases, pubmed-meshheading:11811555-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:11811555-Rolipram, pubmed-meshheading:11811555-Sialoglycoproteins
pubmed:year
2002
pubmed:articleTitle
Involvement of phosphodiesterase isozymes in osteoblastic differentiation.
pubmed:affiliation
Department of Orthopedic Surgery, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't