期刊
CURRENT MEDICINAL CHEMISTRY
卷 15, 期 28, 页码 2984-2990出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/092986708786848695
关键词
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资金
- Ministry of University and Research P.R.I.N./MIUR [PRIN 2006062153_002, 2006068944_001]
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.
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