Estrogen activates cyclin-dependent kinases 4 and 6 through induction of cyclin D in rat primary osteoblasts

Masayo Fujita, Tomohiko Urano, Kuniko Horie, Kazuhiro Ikeda, Tohru Tsukui, Hideoki Fukuoka, Osamu Tsutsumi, Yasuyoshi Ouchi, Satoshi Inoue*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)


Estrogen plays important roles in maintaining bone density and protecting against osteoporosis, but the underlying mechanisms of estrogen action via estrogen receptors (ERs) in bone remain to be clarified. In the present study, we isolated primary osteoblasts derived from transgenic rats harboring a dominant negative ER mutant, rat ERα (1-535) cDNA, and from their wild-type litter-mates. We observed that the rate of cell growth of osteoblasts from the transgenic rats was reduced compared to that of wild-type osteoblasts. Utilizing cDNA microarray analysis, we found that mRNA level of cyclin D2 was lower in the osteoblasts from the transgenic rats. D-type cyclins including cyclin D1, cyclin D2, and cyclin D3 are cell cycle regulators that promote progression through the early-to-mid G1 phase of the cell cycle. The protein levels of D-type cyclins including cyclin D2 and cyclin D3 but not cyclin D1 were elevated in wild-type osteoblasts with 17β-estradiol treatment, resulting in the activation of cyclin-dependent kinases 4 and 6 (Cdk4/6) activities and the promotion of cell growth. Moreover, an anti-estrogen ICI 182,780 abolished the induction of the expression of D-type cyclins by 17β-estradiol. Our findings indicate that estrogen and its receptors enhance Cdk4/6 activities through the induction of D-type cyclins, leading to the growth promotion of osteoblasts.

Original languageEnglish
Pages (from-to)222-228
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number2
Publication statusPublished - 2002
Externally publishedYes


  • Cdk
  • Cyclin D
  • Estrogen
  • Estrogen receptor
  • Microarray
  • Osteoblast

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology


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