RRC ID |
41983
|
Author |
Itoh F, Aoyagi S, Furihata-Komatsu H, Aoki M, Kusama H, Kojima M, Kogo H.
|
Title |
Clodronate stimulates osteoblast differentiation in ST2 and MC3T3-E1 cells and rat organ cultures.
|
Journal |
Eur J Pharmacol
|
Abstract |
We investigated the direct effects of various bisphosphonates on osteoblasts. At 10(-5) M, clodronate increased alkaline phosphatase activity in cultured MC3T3-E1 (osteoblast-like line) and ST2 (pluripotent mesenchymal line) cells. Etidronate significantly increased alkaline phosphatase activity at 10(-5) M only in MC3T3-E1 cells. These effects were due to an increase in alkaline phosphatase-positive cell numbers, and the differentiation-enhanced cells were capable of mineralization (von Kossa stain). Other bisphosphonates (pamidronate, alendronate, and incadronate) did not increase alkaline phosphatase activity in either cell line. In cultured rat calvariae, clodronate stimulated the expression of genes for alkaline phosphatase and osteocalcin (osteoblast-differentiation markers), but decreased the expression of the gene for tartrate-resistant acid phosphatase (osteoclast marker). Clodronate, etidronate, and incadronate inhibited protein Tyr phosphatase and Ser/Thr phosphatase activities in MC3T3-E1 cells. These data suggest that clodronate acts directly on mesenchymal cells to enhance osteoblast differentiation, and this effect may be partly expressed through inhibition of protein Tyr phosphatase and/or Ser/Thr phosphatase activity.
|
Volume |
477(1)
|
Pages |
9-16
|
Published |
2003-9-5
|
DOI |
10.1016/j.ejphar.2003.08.011
|
PII |
S0014299903022052
|
PMID |
14512092
|
MeSH |
Alkaline Phosphatase / metabolism
Animals
Blotting, Northern
Cell Differentiation / drug effects*
Cell Differentiation / genetics
Cells, Cultured
Clodronic Acid / chemistry
Clodronic Acid / pharmacology*
Female
Fetus
Mice
Organ Culture Techniques
Osteoblasts / drug effects*
Osteoblasts / enzymology
Osteoblasts / physiology
Rats
Rats, Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction
Skull / drug effects
Skull / metabolism
Stem Cells / drug effects
Stem Cells / enzymology
Stem Cells / physiology
Time Factors
|
IF |
3.263
|
Times Cited |
35
|
WOS Category
|
PHARMACOLOGY & PHARMACY
|
Resource |
Human and Animal Cells |
MC3T3-E1(RCB1126)
ST2(RCB0224) |