Prostaglandin E2 stimulates DNA synthesis by a cyclic AMP‐independent pathway in osteoblastic clone MC3T3‐E1 cells

Yoshiyuki Hakeda, Takahiko Yoshino, Yoshinori Natakani, Noriyoshi Kurihara, Norihiko Maeda, Masayoshi Kumegawa

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Abstract

The effect of prostaglandin E2 (PGE2) on osteoblastic cell proliferation was investigated using osteoblastic clone MC3T3‐E1 cells cultured in serum‐free medium. PGE2 at 2 μg/ml increased the number of the cells by 2 days after its addition. PGE2 raised the level of DNA synthesis in a dose‐related fashion after a constant lag time, the maximal effect being at 2–10 μg/ml and the level about fourfold over that of the control at 36 hr after its addition. However, at low doses (below 0.2 μg/ml), PGE2 rather depressed DNA synthesis. Isobutyl methylxanthine counteracted the stimulation of DNA synthesis by PGE2, and forskolin depressed the synthesis, which was inversely correlated with increasing intracellular cAMP content. These results indicate that an increase in cAMP content inhibits DNA synthesis. In addition, 2′,5′‐dideoxyadenosine did not negate the stimulatory effect of PGE2 on DNA synthesis, suggesting that PGE2 increases DNA synthesis, probably via a pathway different from the adenylate cyclase/cAMP system. Moreover, at a high dose, PGE2 stimulated both the production and degradation of cAMP; the elevationof cAMP content was rapidly depressed by the stimulated degradation system. Consequently, thestimulatory effect of PGE2 on DNA synthesis would be released from the inhibition by cAMP, resulting in an increase in DNA synthesis. Taken together with data from our previous reports, these results indicate that PGE2 enhances both the proliferation and differentiation of osteoblastic cells in vitro, which are probably mediated by two different second messengers dependent on the concentration of PGE2.

Original languageEnglish (US)
Pages (from-to)155-161
Number of pages7
JournalJournal of Cellular Physiology
Volume128
Issue number2
DOIs
StatePublished - 1986
Externally publishedYes

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Clone cells
Dinoprostone
Clone Cells
DNA
Degradation
Cell proliferation
Second Messenger Systems
Colforsin
Adenylyl Cyclases

ASJC Scopus subject areas

  • Medicine(all)
  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Prostaglandin E2 stimulates DNA synthesis by a cyclic AMP‐independent pathway in osteoblastic clone MC3T3‐E1 cells. / Hakeda, Yoshiyuki; Yoshino, Takahiko; Natakani, Yoshinori; Kurihara, Noriyoshi; Maeda, Norihiko; Kumegawa, Masayoshi.

In: Journal of Cellular Physiology, Vol. 128, No. 2, 1986, p. 155-161.

Research output: Contribution to journalArticle

Hakeda, Yoshiyuki ; Yoshino, Takahiko ; Natakani, Yoshinori ; Kurihara, Noriyoshi ; Maeda, Norihiko ; Kumegawa, Masayoshi. / Prostaglandin E2 stimulates DNA synthesis by a cyclic AMP‐independent pathway in osteoblastic clone MC3T3‐E1 cells. In: Journal of Cellular Physiology. 1986 ; Vol. 128, No. 2. pp. 155-161.
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abstract = "The effect of prostaglandin E2 (PGE2) on osteoblastic cell proliferation was investigated using osteoblastic clone MC3T3‐E1 cells cultured in serum‐free medium. PGE2 at 2 μg/ml increased the number of the cells by 2 days after its addition. PGE2 raised the level of DNA synthesis in a dose‐related fashion after a constant lag time, the maximal effect being at 2–10 μg/ml and the level about fourfold over that of the control at 36 hr after its addition. However, at low doses (below 0.2 μg/ml), PGE2 rather depressed DNA synthesis. Isobutyl methylxanthine counteracted the stimulation of DNA synthesis by PGE2, and forskolin depressed the synthesis, which was inversely correlated with increasing intracellular cAMP content. These results indicate that an increase in cAMP content inhibits DNA synthesis. In addition, 2′,5′‐dideoxyadenosine did not negate the stimulatory effect of PGE2 on DNA synthesis, suggesting that PGE2 increases DNA synthesis, probably via a pathway different from the adenylate cyclase/cAMP system. Moreover, at a high dose, PGE2 stimulated both the production and degradation of cAMP; the elevationof cAMP content was rapidly depressed by the stimulated degradation system. Consequently, thestimulatory effect of PGE2 on DNA synthesis would be released from the inhibition by cAMP, resulting in an increase in DNA synthesis. Taken together with data from our previous reports, these results indicate that PGE2 enhances both the proliferation and differentiation of osteoblastic cells in vitro, which are probably mediated by two different second messengers dependent on the concentration of PGE2.",
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