Expression of inducible cAMP early repressor is coupled to the cAMP-protein kinase A signaling pathway in osteoblasts

J. M. Nervina, S. Tetradis, Y. F. Huang, D. Harrison, Carlos Molina, B. E. Kream

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Abstract

We previously showed that parathyroid hormone (PTH) induces inducible cAMP early repressor (ICER) in osteoblastic cells and mouse calvariae. PTH signaling in osteoblastic cells is transduced by PTH receptor 1, which is coupled to cAMP-protein kinase A (PKA), protein kinase C (PKC). and calcium signaling pathways. In the present study, we examined the role of these pathways in mediating PTH-induced ICER mRNA and protein expression in osteoblastic MC3T3-E1 cells. Using RT-PCR, we found that PTH(1-34), forskolin (FSK), and 8-bromo-cAMP (8Br-cAMP) induced ICER expression, while phorbol myristate acetate (PMA), ionomycin, and PTH(3-34) did not. Similar results were found for the induction of ICER protein. PKA inhibition by H89 markedly reduced PTH- and FSK-induced ICER expression, while PKC depletion by PMA had little effect. We also tested ICER induction by other osteotropic signaling agonists. Other cAMP-PKA pathway activators, such as PTH-related protein (PTHrP), induced ICER expression, while agents that signal through other pathways did not. PTHrP maximally induced ICER mRNA at 2-4 h, which then returned to baseline by 10 h. Finally, PTH, FSK, and PTHrP induced ICER in cultured mouse calvariae and osteoblastic ROS 17/2.8, UMR-106, and Pyla cells. We conclude that ICER expression in osteoblasts requires activation of the cAMP-PKA signaling pathway.

Original languageEnglish
Pages (from-to)483-490
Number of pages8
JournalBone
Volume32
Issue number5
DOIs
StatePublished - 1 Jan 2003

Fingerprint

Cyclic AMP-Dependent Protein Kinases
Parathyroid Hormone
Osteoblasts
Colforsin
Repressor Proteins
Tetradecanoylphorbol Acetate
Skull
Protein Kinase C
Parathyroid Hormone Receptor Type 1
8-Bromo Cyclic Adenosine Monophosphate
Parathyroid Hormone-Related Protein
Messenger RNA
Ionomycin
Calcium Signaling
Proteins
Polymerase Chain Reaction

Keywords

  • Bone
  • ICER
  • Osteoblast
  • Parathyroid hormone
  • cAMP

Cite this

Nervina, J. M. ; Tetradis, S. ; Huang, Y. F. ; Harrison, D. ; Molina, Carlos ; Kream, B. E. / Expression of inducible cAMP early repressor is coupled to the cAMP-protein kinase A signaling pathway in osteoblasts. In: Bone. 2003 ; Vol. 32, No. 5. pp. 483-490.
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abstract = "We previously showed that parathyroid hormone (PTH) induces inducible cAMP early repressor (ICER) in osteoblastic cells and mouse calvariae. PTH signaling in osteoblastic cells is transduced by PTH receptor 1, which is coupled to cAMP-protein kinase A (PKA), protein kinase C (PKC). and calcium signaling pathways. In the present study, we examined the role of these pathways in mediating PTH-induced ICER mRNA and protein expression in osteoblastic MC3T3-E1 cells. Using RT-PCR, we found that PTH(1-34), forskolin (FSK), and 8-bromo-cAMP (8Br-cAMP) induced ICER expression, while phorbol myristate acetate (PMA), ionomycin, and PTH(3-34) did not. Similar results were found for the induction of ICER protein. PKA inhibition by H89 markedly reduced PTH- and FSK-induced ICER expression, while PKC depletion by PMA had little effect. We also tested ICER induction by other osteotropic signaling agonists. Other cAMP-PKA pathway activators, such as PTH-related protein (PTHrP), induced ICER expression, while agents that signal through other pathways did not. PTHrP maximally induced ICER mRNA at 2-4 h, which then returned to baseline by 10 h. Finally, PTH, FSK, and PTHrP induced ICER in cultured mouse calvariae and osteoblastic ROS 17/2.8, UMR-106, and Pyla cells. We conclude that ICER expression in osteoblasts requires activation of the cAMP-PKA signaling pathway.",
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Expression of inducible cAMP early repressor is coupled to the cAMP-protein kinase A signaling pathway in osteoblasts. / Nervina, J. M.; Tetradis, S.; Huang, Y. F.; Harrison, D.; Molina, Carlos; Kream, B. E.

In: Bone, Vol. 32, No. 5, 01.01.2003, p. 483-490.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Tetradis, S.

AU - Huang, Y. F.

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AU - Molina, Carlos

AU - Kream, B. E.

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