Molecular Actions of Parathyroid Hormone

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.