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Related Experiment Videos

Cyclic AMP-dependent and calcium-dependent signals in parathyroid hormone function.

R Civitelli1, K A Hruska, V Shen

  • 1Division of Endocrinology and Bone Metabolism, Jewish Hospital of St. Louis, Washington University Medical Center, Missouri 63110.

Experimental Gerontology
|January 1, 1990
PubMed
Summary

Parathyroid hormone (PTH) primarily uses cAMP signaling to regulate osteoblast growth and bone resorption. However, calcium (Ca2+) and protein kinase C (PKC) activation are also essential for a complete PTH response.

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Endocrinology

Background:

  • Parathyroid hormone (PTH) is known to activate both cyclic adenosine monophosphate (cAMP) and calcium/protein kinase C (PKC) signaling pathways.
  • The distinct roles of these two signaling cascades in regulating osteoblastic functions remain to be fully elucidated.

Purpose of the Study:

  • To investigate the specific contributions of cAMP-dependent and Ca2+-dependent signals in mediating PTH's effects on osteoblastic cell proliferation and bone resorption.
  • To determine the synergistic or independent actions of these signaling pathways in response to PTH.

Main Methods:

  • Utilized UMR 106-01 osteogenic sarcoma cells and fetal rat limb bone cultures.
  • Administered PTH, dibutyryl-cAMP (dbcAMP), forskolin, Ca2+ ionophore ionomycin, and phorbol 12-myristate 13-acetate (PMA).

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  • Assessed [3H] thymidine incorporation for cell proliferation and 45Ca release for bone resorption.

    • Main Results:

    • PTH significantly inhibited [3H] thymidine incorporation, an effect mimicked by dbcAMP and forskolin.
    • Ionomycin and PMA showed minimal effects on proliferation alone but enhanced the inhibitory effects of dbcAMP, indicating synergism.
    • Both dbcAMP and ionomycin stimulated 45Ca release, with their combination fully reproducing the PTH effect, suggesting synergistic action.

    Conclusions:

    • PTH-mediated regulation of osteoblastic cell proliferation and bone resorption is primarily driven by the cAMP signaling pathway.
    • Activation of the Ca2+/PKC signaling pathway is crucial for achieving the full hormonal response of PTH in both cellular and organ culture systems.