Targeting Vascular Niche by Parathyroid Hormone

Authors: Pagliarulo, Caterina; Salvatore, Paola; Napoli, Claudio

Source: Current Medicinal Chemistry, Volume 15, Number 28, December 2008 , pp. 2984-2990(7)

Publisher: Bentham Science Publishers

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Abstract:

Currently, the parathyroid hormone (PTH) is a drug approved for use in humans only in bone metabolism diseases, as the osteoporosis. The PTH acts primarily by binding to its principal receptor, PTH/PTHrP-R, a member of the class B G protein-coupled receptor (GPCR) family that includes together receptors for other therapeutically important peptide hormones. PTH plays a central role in the maintenance of calcium and phosphate homeostasis and bone health. It acts to maintain bone and mineral homeostasis through several mechanisms: elevation of blood calcium by increasing osteoclastic bone resorption; enhancement of renal calcium reabsorption; stimulation of renal 1,25-dihydroxyvitamin D synthesis, leading to increased intestinal calcium absorption; and promotion of phosphaturia via inhibition of renal tubular transepithelial phosphate reabsorption .

However, many findings indicate that the PTH could be a future drug essential in therapy of cardiovascular diseases through multiple effects on hematopoietic stem cells niche. In adult bone marrow, the hamatopoietic stem cells are located in the trabecular endosteum (osteoblastic niche) or sinusoidal perivascular areas (vascular niche). A plausible function for the vascular niche is to assist hematopoietic stem cells in transendothelial migration, which is important during both homing and mobilization. Indeed, in experimental models, PTH treatment increases migration of angiogenic CD45+/CD34+ progenitor cells to the hindlimb ischemia as well as in the ischemic heart, promoting tissue repair by enhanced neovascularization and cell survival.

Keywords: Vascular Niche; Parathyroid Hormone; osteoporosis; peptide hormones; phosphate homeostasis; hematopoietic stem cells; cardiovascular diseases; hindlimb ischemia

Document Type: Research article

DOI: http://dx.doi.org/10.2174/092986708786848695

Affiliations: 1: Department of General Pathology, 1st School of Medicine, II University of Naples, Complesso S. Andrea delle Dame,Via De Crecchio 7, 80138 Naples, Italy.

Publication date: 2008-12-01

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Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

Targeting Vascular Niche by Parathyroid Hormone

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