Description
PTH (parathyroid hormone) is an endogenous peptide hormone that binds PTH1/2 receptors and exhibits anti-osteoporotic, anti-angiogenic, and pro-fibrotic activities. PTH (1-34) is clinically used to treat osteoporosis, as it promotes bone formation, increases bone mineral density, enhances bone strength, and improves bone biomechanical properties. In vivo, PTH downregulates expression of collagen type 1 and RANKL and also decreases activity of osteoblasts. PTH activates PKA signaling to inhibit angiogenesis in vitro in an HSP70-mediated manner but also promotes the epithelial-to-mesenchymal transition (EMT) in vitro and in vivo, potentially enhancing cancer aggressiveness and metastasis. Additionally, PTH promotes fibrosis by activating hepatic stellate cells and increasing levels of matrix metalloproteinase 2 (MMP2), collagen, TGF-β, and α-SMC in vitro.
References
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Augustine M, Horwitz MJ. Parathyroid hormone and parathyroid hormone-related protein analogs as therapies for osteoporosis. Curr Osteoporos Rep. 2013 Dec;11(4):400-6. PMID: 24078470.
Liang FF, Liu CP, Li LX, et al. Activated effects of parathyroid hormone-related protein on human hepatic stellate cells. PLoS One. 2013 Oct 7;8(10):e76517. PMID: 24116114.
Xu J, Rong H, Ji H, et al. Effects of different dosages of parathyroid hormone-related protein 1-34 on the bone metabolism of the ovariectomized rat model of osteoporosis. Calcif Tissue Int. 2013 Sep;93(3):276-87. PMID: 23807531.
Saini V, Marengi DA, Barry KJ, et al. Parathyroid hormone (PTH)/PTH-related peptide type 1 receptor (PPR) signaling in osteocytes regulates anabolic and catabolic skeletal responses to PTH. J Biol Chem. 2013 Jul 12;288(28):20122-34. PMID: 23729679.
Grzesiak JJ, Smith KC, Chalberg C, et al. Heat shock protein-70 expressed on the surface of cancer cells binds parathyroid hormone-related protein in vitro. Endocrinology. 2005 Aug;146(8):3567-76. PMID: 15878959.
Bakre MM, Zhu Y, Yin H, et al. Parathyroid hormone-related peptide is a naturally occurring, protein kinase A-dependent angiogenesis inhibitor. Nat Med. 2002 Sep;8(9):995-1003. PMID: 12185361.
