Transforming growth factor-beta modulates proliferation and differentiation of mouse clonal osteoblastic MC3T3-E1 cells depending on their maturation stages.
The effect of transforming growth factor-beta (TGF-beta) on proliferation and differentiation of mouse clonal osteoblastic cells (MC3T3-E1) was examined in vitro in three different stages of their differentiation. Stage I (1-3 days after plating) was characterized by rapid cell growth, negligible alkaline phosphatase (ALP) activity and high proteoglycan synthesis, but low collagen production. In stage II (3-5 days after plating), proteoglycan synthesis sharply decreased and ALP activity and collagen synthesis began to increase. Stage III (7-9 days after plating) was characterized by maximal osteoblastic phenotypes. Treating MC3T3-E1 cells with 1 ng/ml of TGF-beta greatly inhibited DNA synthesis in stage I but not in stage II. In contrast, TGF-beta dose-dependently stimulated the synthesis of collagenase digestible proteins (CDP), noncollagenous proteins (NCP) and proteoglycan, especially in stage II. The minimum effective dose of TGF-beta in this stage was as low as 0.04-0.2 ng/ml. In stages I and III, the MC3T3-E1 cells were rather insensitive to TGF-beta in increasing three osteoblastic phenotypes. The increase in ALP activity in stages II and III was inhibited by 1 ng/ml of TGF-beta. These results indicate that the response to TGF-beta of mouse clonal osteoblastic MC3T3-E1 cells changes depending on their maturation stages.
Katagiri
T
T
School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Lee
T
T
Takeshima
H
H
Suda
T
T
Tanaka
H
H
Omura
S
S
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003094:Collagen / Q000096:biosynthesis; D004247:DNA / Q000096:biosynthesis; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010641:Phenotype; D011509:Proteoglycans / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D011509:Proteoglycans; D016212:Transforming Growth Factor beta; D003094:Collagen; D004247:DNA; D000469:Alkaline Phosphatase