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Signal transduction pathways mediating parathyroid hormone regulation of osteoblastic gene expressionParathyroid hormone (PTH) plays a central role in regulation of calcium metabolism. For example, excessive or inappropriate production 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 activation 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.
Document ID
20050000334
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
External Source(s)
Authors
Partridge, N. C.
(St. Louis University School of Medicine Missouri 63104)
Bloch, S. R.
Pearman, A. T.
Date Acquired
August 22, 2013
Publication Date
July 1, 1994
Publication Information
Publication: Journal of cellular biochemistry
Volume: 55
Issue: 3
ISSN: 0730-2312
Subject Category
Life Sciences (General)
Distribution Limits
Public
Copyright
Other
Keywords
Review
NASA Discipline Musculoskeletal
Review, Tutorial
Non-NASA Center

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