Signal transduction pathways mediating parathyroid hormone regulation of osteoblastic gene expression

Nicola Partridge, S. R. Bloch, A. T. Pearman

Research output: Contribution to journalArticle

Abstract

Parathyroid hormone (PTH) plays a central role in regulation of calcium metabolism. For example, excessive or inappropriate product;on of PTH or the related hormone, parathyroid hormone related protein (PTHrP), accounts for the majority of the causes of hypercalcemia. Both hormones act through the same receptor on the osteoblast to elicit enhanced bone resorption by the osteoclast. Thus, the osteoblast mediates the effect of PTH in the resorption process. In this process, PTH causes a change in the function and phenotype of the osteoblast from a cell involved in bone formation to one directing the process of bone resorption. In response to PTH, the osteoblast decreases collagen, alkaline phosphatase, and osteopontin expression and increases production of osteocalcin, cytokines, and neutral proteases. Many of these changes have been shown to be due to effects on mRNA abundance through either transcriptional or post-transcriptional mechanisms. However, the signal transduction pathway for the hormone to cause these changes is not completely elucidated in any case. Binding of PTH and PTHrP to their common receptor has been shown to result in activation of protein kinases A and C and increases in intracellular calcium. The latter has not been implicated in any changes in mRNA of osteoblastic genes. On the other hand act;vat;on of PKA can mimic all the effects of PTH; protein kinase C may be involved in some responses. We will discuss possible mechanisms linking PKA and PKC activation to changes in gene expression, particularly at the nuclear level.

Original languageEnglish (US)
Pages (from-to)321-327
Number of pages7
JournalJournal of Cellular Biochemistry
Volume55
Issue number3
DOIs
StatePublished - 1994

Fingerprint

Signal transduction
Gene Expression Regulation
Parathyroid Hormone
Gene expression
Signal Transduction
Osteoblasts
Parathyroid Hormone-Related Protein
Bone
Hormones
Bone Resorption
Protein Kinase C
Chemical activation
Calcium
Messenger RNA
Osteopontin
Osteocalcin
Hypercalcemia
Osteoclasts
Cyclic AMP-Dependent Protein Kinases
Metabolism

Keywords

  • Activator protein-1
  • cAMP
  • Gene expression
  • Osteoblasts
  • Parathyroid hormone
  • Signal transduction

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

Signal transduction pathways mediating parathyroid hormone regulation of osteoblastic gene expression. / Partridge, Nicola; Bloch, S. R.; Pearman, A. T.

In: Journal of Cellular Biochemistry, Vol. 55, No. 3, 1994, p. 321-327.

Research output: Contribution to journalArticle

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