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عنوان فارسی مقاله:

هورمون پاراتیروئید باعث بیان و پروتئولیتیک پردازش رنکل در استئوبلاست موش اولیه میشود


عنوان انگلیسی مقاله:

Parathyroid hormone induces expression and proteolytic processing of Rankl in primary murine osteoblasts


سال انتشار : 2016



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مقدمه انگلیسی مقاله:

1. Introduction

One of the most important regulatory systems controlling bone remodeling involves receptor activator of nuclear factor κB (Rank), its ligand (Rankl) and the Rankl decoy receptor osteoprotegerin (Opg) [1]. More specifically, Rankl expressed by cells of the osteoblast lineage is known to activate osteoclastogenesis from hematopoietic progenitors after binding to Rank in a Traf6-dependent manner [2]. The physiological relevance of the Rankl-Rank interaction is probably best underscored by the fact that mutations in either gene causes osteoclast-poor osteopetrosis in humans [3]. Likewise, the therapeutic relevance of the system is highlighted by the fact that Denosumab, a monoclonal antibody neutralizing human RANKl, has been successfully introduced as an anti-resorptive drug for the treatment of individuals with osteoporosis or osteolytic bone destruction [4]. Molecularly, the Rankl-Rank-Opg-system has been extensively studied through a combination of mouse genetics and tissue culture experiments. Interestingly however, one aspect of Rankl biology is still not fully understood, as Rankl is synthesized as a type II transmembrane protein that can be proteolytically processed to generate a soluble form (sRankl) [5]. In fact, since the majority of published studies either analyzed expression of the Rankl-encoding gene (i.e. Tnsfsf11) or the extracellular presence of soluble Rankl (sRankl), the question about its proteolytical processing was not generally addressed. Moreover, since the previously identified cleavage sites for putative Rankl sheddases (Adam10, Adam17 or Mmp14) are all located within a region of the murine Rankl protein that is not conserved in human RANKl (Fig. S1), it is at least debatable, if the findings obtained by forced expression studies are physiologically relevant [6–8]. Our interest in this particular question was triggered by a previous study, where we analyzed the molecular effects of the cytokine IL-33 on bone remodeling. More specifically we found that IL-33 acts as a potent inhibitor of osteoclastogenesis, both in vitro and in vivo [9,10]. The physiological relevance of this finding was supported by the analysis of mice lacking the IL-33 receptor, which displayed increased osteoclast indices, assessed by cellular histomorphometry on bone sections [9]. In the context of this study we additionally analyzed the influence of IL-33 on primary osteoblasts. Whereas chronic IL-33 administration during the course of differentiation did not interfere with matrix mineralization, a short-term treatment of primary osteoblasts with IL-33 induced the expression of several genes potentially affecting bone remodeling, including Tnfsf11. Interestingly however, and potentially explaining the absence of a pro-osteoclastogenic effect of IL-33, we failed to detect sRankl in the medium of osteoblasts after treatment with IL-33. In contrast, in the context of analyzing a mouse model with mucolipidosis-II, we found that sRankl was detectable in the medium of primary osteoblasts following treatment with PTH for 6 h [11]. This apparent inconsistency led us to directly compare the effects of IL-33 and PTH on Tnfsf11 expression and sRankl release.



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کلمات کلیدی:

Parathyroid hormone induces expression of the inducible ... - NCBI - NIH https://www.ncbi.nlm.nih.gov/pubmed/9844102 by S Tetradis - ‎1998 - ‎Cited by 33 - ‎Related articles J Bone Miner Res. 1998 Dec;13(12):1846-51. Parathyroid hormone induces expression of the inducible cAMP early repressor in osteoblastic MC3T3-E1 cells ... Parathyroid hormone induces expression and ... - ScienceDirect www.sciencedirect.com/science/article/pii/S8756328216302368 by T Heckt - ‎2016 - ‎Cited by 3 - ‎Related articles Highlights. •. Treatment of murine osteoblasts with IL-33 and PTH differentially affects expression and proteolytic processing of Rankl. •. The PTH-induced ... Parathyroid Hormone Stimulates Osteoblastic Expression of MCP-1 to ... www.jbc.org/content/282/45/33098.full by X Li - ‎2007 - ‎Cited by 133 - ‎Related articles Nov 9, 2007 - Our model suggests that PTH-induced osteoblastic expression of MCP-1 is involved in recruitment and differentiation at the stage of ... Parathyroid hormone - Wikipedia https://en.wikipedia.org/wiki/Parathyroid_hormone Parathyroid hormone (PTH), also called parathormone or parathyrin, is a hormone secreted by ... Binding stimulates osteoblasts to increase their expression of RANKL and inhibits their secretion of Osteoprotegerin (OPG). Free OPG ... Parathyroid Hormone Induces Expression of the ... - Wiley Online Library onlinelibrary.wiley.com/doi/10.1359/jbmr.1998.13.12.1846/abstract by S Tetradis - ‎1998 - ‎Cited by 33 - ‎Related articles Dec 1, 1998 - Abstract. Parathyroid hormone (PTH) regulates gene expression in skeletal osteoblasts mainly through the cAMP–protein kinase A (PKA) ... Principles of Bone Biology - Page 656 - Google Books Result https://books.google.com/books?isbn=0080568750 John P. Bilezikian, ‎Lawrence G. Raisz, ‎T. John Martin - 2008 - ‎Medical Parathyroid hormone induces expression of the nuclear orphan receptor Nurr1 in bone cells. Endocrinology. 142(2): 663–670. Tetradis, S. et al. (2001). The Parathyroids: Basic and Clinical Concepts https://books.google.com/books?isbn=0123977908 John P. Bilezikian, ‎Robert Marcus, ‎Michael A. Levine - 2014 - ‎Medical Parathyroid hormone and parathyroid hormone-related protein exert both pro- and ... Parathyroid hormone induces expression of the inducible cAMP early ... Principles of Bone Biology, Two-Volume Set https://books.google.com/books?isbn=0080539602 John P. Bilezikian, ‎Lawrence G. Raisz, ‎Gideon A. Rodan - 2002 - ‎Medical Parathyroid hormone stimulates electrogenic sodium transport in A6 cells. ... Long-term effects of parathyroidectomy for primary hyperparathyroidism on arterial ...