Molecular Actions of Parathyroid Hormone

doi:10.1016/B978-0-12-397166-1.00007-2

The Parathyroids (Third Edition)

Basic and Clinical Concepts

2015, Pages 119-126

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Abstract

Parathyroid hormone (PTH) has manifold actions on osteogenic cells, affecting their differentiation, function, proliferation, and survival. While PTH has been known to activate the cAMP/protein kinase A (PKA) pathway since the early 1980s, we now recognize that engagement of the hormone with its receptors triggers a complex variety of signaling cascades, including Ca²⁺/protein kinase C (PKC), Wnt/β-catenin, and mitogen-activated protein kinase (MAPK), resulting in an intricate web of downstream events involving signaling molecules and transcription factors. These series of events eventually lead to modulation of genes crucial for osteoblast differentiation, function, cell division, and apoptosis. Considering the diversity of PTH actions on bone such complexity is not surprising. PTH continues to challenge researchers with its multifaceted and not yet entirely known effects on bone cells.

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Cited by (3)

Parathyroid hormone: Anabolic and catabolic actions on the skeleton
2015, Current Opinion in Pharmacology
Citation Excerpt :
These results are controversial, and further studies are necessary to elucidate the role of Dkk1 as a mediator of the PTH actions on bone formation. EphrinB2 is a membrane-tethered ligand that interacts with its receptor EphB4, resulting in a two-way signaling between two adjacent cells [120]. PTH induces the expression of EphrinB2 in osteoblasts, stimulating Ephrin-mediated interaction between two osteoblastic cells, and thereby increasing PTH-induced bone formation [121].
Parathyroid hormone (PTH) is essential for the maintenance of calcium homeostasis through, in part, its actions to regulate bone remodeling. While PTH stimulates both bone formation and bone resorption, the duration and periodicity of exposure to PTH governs the net effect on bone mass, that is whether it is catabolic or anabolic. PTH receptor signaling in osteoblasts and osteocytes can increase the RANKL/OPG ratio, increasing both osteoclast recruitment and osteoclast activity, and thereby stimulating bone resorption. In contrast, PTH-induced bone formation is explained, at least in part, by its ability to downregulate SOST/sclerostin expression in osteocytes, permitting the anabolic Wnt signaling pathway to proceed. The two modes of administration of PTH, that is, continuous vs. intermittent, can regulate, in bone cells, different sets of genes; alternatively, the same sets of genes exposed to PTH in sustained vs. transient way, will favor bone resorption or bone formation, respectively. This article reviews the effects of PTH on bone cells that lead to these dual catabolic and anabolic actions on the skeleton.
The role of hormones in bone regulation and regeneration
2018, Bone Regeneration: Concepts, Clinical Aspects and Future Directions
Primary hyperparathyroidism
2018, Journal of Clinical Endocrinology and Metabolism

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Chapter 7 - Molecular Actions of Parathyroid Hormone

Abstract