Parathyroid Hormone Induction of Cyclooxygenase-2 in Murine Osteoblasts: Role of the Calcium-Calcineurin-NFAT Pathway
2010

How Parathyroid Hormone Affects Bone Cells

publication Evidence: moderate

Author Information

Author(s): Huang Hechang, Chikazu Daichi, Voznesensky Olga S, Herschman Harvey R, Kream Barbara E, Drissi Hicham, Pilbeam Carol C

Primary Institution: University of Connecticut Health Center

Hypothesis

Parathyroid hormone induces COX-2 transcription in murine osteoblastic cells via both CRE- and NFAT/AP-1–binding sites.

Conclusion

The study shows that parathyroid hormone activates the calcium-calcineurin-NFAT signaling pathway, which is important for COX-2 expression in osteoblasts.

Supporting Evidence

  • PTH stimulates COX-2 expression in osteoblasts via the cAMP-PKA pathway.
  • Mutations in the NFAT and AP-1 sites significantly reduce PTH-stimulated COX-2 promoter activity.
  • Calcium chelation and calcineurin inhibitors significantly inhibit PTH-induced COX-2 expression.
  • NFATc1 overexpression enhances COX-2 expression in osteoblasts.

Takeaway

Parathyroid hormone helps bone cells make a substance called COX-2, which is important for bone health, by using two special pathways in the cell.

Methodology

The study involved stable transfection of murine osteoblastic cells with luciferase reporter constructs and measurement of luciferase activity in response to parathyroid hormone treatment.

Limitations

The variability in basal activity among experiments suggests potential phenotypic differences in the cell lines used.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1359/jbmr.091019

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