Endothelin Receptors, Second Messengers, and Actions in Bone

Stern, Paula H.; Tatrai, Agnes; Semler, David E.; Lee, Suk Kyeong; Lakatos, Péter; Strieleman, Paul J.; Tarján, Gábor; Sanders, J. L.

doi:10.1093/jn/125.suppl_7.2028s

Cited by 72 publications

(43 citation statements)

References 19 publications

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“…Osteoblasts express both the endothelin-A (ET A ) and ET B receptors [70][71][72]. Stimulation of these receptors by endothelin-1 (ET-1) triggers mitogenesis of osteoblasts.…”

Section: Microenvironment Of Bone Metastasesmentioning

confidence: 99%

Proteases as modulators of tumor–stromal interaction: Primary tumors to bone metastases

Wilson

Singh

2008

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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SummaryAs cells undergo oncogenic transformation and as transformed cells arrive at metastatic sites, a complex interplay occurs with the surrounding stroma. This dialogue between tumor and stroma ultimately dictates the success of the tumor cells in the given microenvironment. As a result, understanding the molecular mechanisms at work is important for developing new therapeutic modalities. Proteases are major players in the interaction between tumor and stroma. This review will focus on the role of proteases in modulating tumor-stromal interactions of both primary breast and prostate tumors as well as at bone metastatic sites in a way that favors tumor growth.

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“…Osteoblasts express both the endothelin-A (ET A ) and ET B receptors [70][71][72]. Stimulation of these receptors by endothelin-1 (ET-1) triggers mitogenesis of osteoblasts.…”

Section: Microenvironment Of Bone Metastasesmentioning

confidence: 99%

Proteases as modulators of tumor–stromal interaction: Primary tumors to bone metastases

Wilson

Singh

2008

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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“…This phenomenon could result from the ET-1 as a paracrine/autocrine factor in cardiovascular tissues. ET-1 was reported to modulate bone metabolism both in vivo and in vitro (37)(38). ET-1 time-and dose-dependently stimulated Na-dependent Pi transport in mouse calvaria-derived osteoblastlike MC3T3-E1 cells.…”

Section: Discussionmentioning

confidence: 98%

Ghrelin reduces rat myocardial calcification induced by nicotine and vitamin D3 in vivo

Wang

Jiang²,

Tang³

et al. 2011

Int J Mol Med

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Abstract. Ghrelin, a newly discovered bioactive peptide, initially was identified as a strong stimulant for the release of growth hormone (GH) and that has improved cardiac function in patients suffering from end-stage chronic heart failure. Increasing evidence has demonstrated that ghrelin may have myocardial protective effects. However, the role of ghrelin in the pathogenesis of cardiovascular diseases remains unclear. In this study, an in vivo model of rat myocardial calcification induced by vitamin D3 and nicotine was used to study the possible mechanism in the regulatory action of ghrelin on the calcified myocardium. Calcification increased total Ca 2+ content and 45 Ca 2+ deposition in the myocardium and alkaline phosphatase (ALP) activation in the plasma. Compared with the control group, ghrelin mRNA expression was up-regulated and the myocardium calcium content was significantly increased in vitamin D3 and nicotine-treated rats. Rats were subcutaneously injected with 1 or 10 nmol/kg ghrelin. Rats treated with both low-and high-dose ghrelin decreased total Ca 2+ content and 45 Ca 2+ deposition in cardiac muscle and inhibited ALP activation in the myocardium and plasma, in a concentration-dependent manner. In addition, osteopontin (OPN) mRNA expression significantly decreased and that of endothelin (ET-1) significantly increased with myocardial calcification. Ghrelin treatment increased OPN expression at the mRNA level and reduced ET-1 mRNA expression in a dose-dependent manner. These results indicate that exogenous administration with ghrelin attenuates myocardial calcification induced by nicotine and vitamin D3, and that the possible mechanism is via the ghrelin-induced increase in the OPN mRNA levels and decrease in the ET-1 mRNA expression in the myocardium.

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“…In this set of experiments, we used endothelin to stimulate G q signaling. Endothelin and its receptors are present and functional in both osteoblasts and osteosarcoma cells, and activation of endothelin receptors leads to robust accumulation of inositol phosphates in these cells (35)(36)(37).…”

Section: Figure 1 Regulation Of Rgs2 Protein Expression In Osteoblastsmentioning

confidence: 99%

Up-regulation of Endogenous RGS2 Mediates Cross-desensitization between Gs and Gq Signaling in Osteoblasts

Roy

Nunn

Hong

et al. 2006

Journal of Biological Chemistry

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Regulator of G protein signaling (RGS) proteins limitG protein-coupled receptors (GPCRs) 6 respond to a variety of hormones, paracrine factors, and neurotransmitters by activating heterotrimeric G proteins. Upon activation of the G protein, G␣ is stimulated to exchange bound GDP for cytosolic GTP and is thought to subsequently dissociate from the ␤␥ dimer. Both G␣ and the ␤␥ dimer are then capable of interacting with cellular effectors for a period of time that is limited by the intrinsic GTPase activity of the G␣ subunit. Regulator of G protein signaling (RGS) proteins can reduce the duration of these interactions by increasing the rate of GTP hydrolysis by the G␣ subunits, or by otherwise blocking interactions between G␣ and its target enzymes through a poorly understood process sometimes referred to as "effector antagonism" (1, 2).G protein signaling in osteoblasts is a critical regulator of bone formation. The predominant GPCRs expressed by osteoblasts include the parathyroid hormone (PTH)/parathyroid hormone-related peptide (PTHrP) receptor type 1 (PTH1R), P2Y nucleotide receptors, and prostaglandin receptors (3). Other GPCRs found in osteoblasts include endothelin, adenosine, ␤-adrenergic, angiotensin II, and calcium-sensing receptors (3, 4). Binding of PTH to its specific receptor, PTH1R, predominantly leads to the activation of G s (although under certain conditions the receptor can also couple to G q and G i ) (5, 6). Activated G s stimulates adenylyl cyclase to generate intracellular cAMP, which results in the activation of protein kinase A. Stimulation of G q promotes the activity of phospholipase C-␤ (PLC-␤), resulting in the accumulation of inositol 1,4,5-trisphosphate and diacylglycerol, which lead, respectively, to release of calcium from intracellular stores and activation of protein kinase C. Nucleotide stimulation of P2Y receptors in osteoblasts results in PLC-␤ activation and calcium mobilization, with no effect on adenylyl cyclase (3, 7).

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Endothelin Receptors, Second Messengers, and Actions in Bone

Cited by 72 publications

References 19 publications

Proteases as modulators of tumor–stromal interaction: Primary tumors to bone metastases

Proteases as modulators of tumor–stromal interaction: Primary tumors to bone metastases

Ghrelin reduces rat myocardial calcification induced by nicotine and vitamin D3 in vivo

Up-regulation of Endogenous RGS2 Mediates Cross-desensitization between Gs and Gq Signaling in Osteoblasts

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