Protein phosphatase inhibitors, okadaic acid and calyculin A, induce alkaline phosphatase activity in osteoblastic cells derived from newborn mouse calvaria.
To determine whether protein phosphatases can affect bone regulation, we examined the effects of okadaic acid (OA) and calyculin A (CA), specific inhibitors of protein phosphatases type 1 and type 2A, on alkaline phosphatase activity of mouse osteoblastic cells. Clone MC3T3-E1 cells were cultured with varying concentrations of OA and CA. OA and CA stimulated alkaline phosphatase (ALP) activity in the cells in dose-dependent fashion with a maximal effect at concentrations of 5 nM and 2 nM, respectively. The properties of OA-induced and native ALP in the cells were the same and they were liver-bone-kidney type. These results show that protein phosphatase inhibitors stimulate bone formation in vitro and that phosphorylation and dephosphorylation of specific proteins in the cells may be involved in bone regulation in vivo as well.
Murata
T
T
Department of Oral Anatomy, Kyushu Dental College, Kitakyushu, Japan.
Shirakawa
S
S
Takehara
T
T
Kobayashi
S
S
Haneji
T
T
D000469:Alkaline Phosphatase / Q000096:biosynthesis* / Q000378:metabolism; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002999:Clone Cells; D004790:Enzyme Induction; D004795:Enzyme Stability; D004988:Ethers, Cyclic / Q000494:pharmacology*; D008387:Marine Toxins; D051379:Mice; D019319:Okadaic Acid; D010006:Osteoblasts / Q000201:enzymology*; D010080:Oxazoles / Q000494:pharmacology*; D010641:Phenotype; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D010766:Phosphorylation / Q000187:drug effects; D012886:Skull; D013696:Temperature
D000596:Amino Acids; D004988:Ethers, Cyclic; D008387:Marine Toxins; D010080:Oxazoles; D019319:Okadaic Acid; C059041:calyculin A; D000469:Alkaline Phosphatase; D010749:Phosphoprotein Phosphatases