Extracellular calcium elicits a chemokinetic response from monocytes in vitro and in vivo

Olszak, Ivona T.; Poznansky, Mark C.; Evans, Richard H.; Olson, Douglas P.; Kos, Claudine H.; Pollak, Martin R.; Brown, Edward M.; Scadden, David T.

doi:10.1172/jci9799

Cited by 138 publications

(125 citation statements)

References 28 publications

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“…Over the past decade, the CaSR has been identified as a novel molecular player in the determination of cellular fate with a fundamental impact on proliferation, apoptosis and differentiation in a diverse array of tissues [2][3][4][5][6][7][8][9][10]. The CaSR coordinates these activities through regulation of a myriad of signaling pathways, including EGFR signaling, MAPK cascades and Ecadherin signaling [3,36,37,47,[50][51][52][62][63][64].…”

Section: Discussionmentioning

confidence: 99%

“…levels, regulating diverse processes such as hormone secretion, gene expression, ion channel activity, inflammation, and control of cellular fate. Here, we will review the recent findings regarding the physiological effects of CaSR activity on the regulation of cellular fate, particularly in the context of proliferation, differentiation and apoptosis [2][3][4][5][6][7][8][9][10]. We will discuss how CaSR signaling determines cellular fate during normal development and how dysregulated signaling might promote the pathogenesis of many diseases, ranging from proliferative to neurodegenerative and vascular diseases.…”

Section: Introductionmentioning

confidence: 99%

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The Calcium-Sensing Receptor as a Regulator of Cellular Fate in Normal and Pathological Conditions

Diez-Fraile¹,

Lammens²,

Benoit³

et al. 2013

Current Molecular Medicine

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Abstract:The calcium-sensing receptor (CaSR) belongs to the evolutionarily conserved family of plasma membrane G protein-coupled receptors (GPCRs). Early studies identified an essential role for the CaSR in systemic calcium homeostasis through its ability to sense small changes in circulating calcium concentration and to couple this information to intracellular signaling pathways that influence parathyroid hormone secretion. However, the presence of CaSR protein in tissues is not directly involved in regulating mineral ion homeostasis points to a role for the CaSR in other cellular functions including the control of cellular proliferation, differentiation and apoptosis. This position at the crossroads of cellular fate designates the CaSR as an interesting study subject is likely to be involved in a variety of previously unconsidered human pathologies, including cancer, atherosclerosis and Alzheimer's disease. Here, we will review the recent discoveries regarding the relevance of CaSR signaling in development and disease. Furthermore, we will discuss the rational for developing and using CaSR-based therapeutics.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Calcium-Sensing Receptor as a Regulator of Cellular Fate in Normal and Pathological Conditions

Diez-Fraile¹,

Lammens²,

Benoit³

et al. 2013

Current Molecular Medicine

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“…Olszak et al (2000) showed that a functional CaR on peripheral blood monocytes (Yamaguchi et al, 1998b) transduces a rise in ambient calcium into a chemotactic response to the chemokine MCP-1 (monocyte chemoattractant protein 1). It does so by upregulating its cognate receptor, CCR2 (chemokine (C-C motif) receptor 2).…”

Section: Infectious Diseasesmentioning

confidence: 99%

Vitamin D and calcium insufficiency-related chronic diseases: molecular and cellular pathophysiology

Peterlik¹,

Cross²

2009

Eur J Clin Nutr

101

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A compromised vitamin D status, characterized by low 25-hydroxyvitamin D (25-(OH)D) serum levels, and a nutritional calcium deficit are widely encountered in European and North American countries, independent of age or gender. Both conditions are linked to the pathogenesis of many degenerative, malignant, inflammatory and metabolic diseases. Studies on tissue-specific expression and activity of vitamin D metabolizing enzymes, 25-(OH)D-1a-hydroxylase and 25-(OH)D-24-hydroxylase, and of the extracellular calcium-sensing receptor (CaR) have led to the understanding of how, in non-renal tissues and cellular systems, locally produced 1,25-dihydroxyvitamin D 3 (1,25-(OH) 2 D 3 ) and extracellular Ca 2 þ act jointly as key regulators of cellular proliferation, differentiation and function. Impairment of cooperative signalling from the 1,25-(OH) 2 D 3 -activated vitamin D receptor (VDR) and from the CaR in vitamin D and calcium insufficiency causes cellular dysfunction in many organs and biological systems, and, therefore, increases the risk of diseases, particularly of osteoporosis, colorectal and breast cancer, inflammatory bowel disease, insulin-dependent diabetes mellitus type I, metabolic syndrome, diabetes mellitus type II, hypertension and cardiovascular disease. Understanding the underlying molecular and cellular processes provides a rationale for advocating adequate intake of vitamin D and calcium in all populations, thereby preventing many chronic diseases worldwide.

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“…The soluble Ca 2+ concentration is approximately 1.1-1.3 mM in the extracellular fluids of tissues (Breitweiser, 2008) and 2.5 mM in blood (Bronner, 1997). Evidence suggests that free extracellular Ca 2+ might play a role as a chemoattractant in addition to cell-type-specific chemoattractants in a variety of developmental processes, including embryonic development (Adams et al, 2006;Chattopadhyay et al, 2007;Reitz et al, 1977), wound healing (Menon et al, 1985;Morris and Chan, 2007), angiogenesis (Aguirre et al, 2010), the immune response (Olszak et al, 2000) and tissue maintenance (Quarles et al, 1997). For example, mammalian gonadotropin-releasing hormone (GnRH) neurons undergo chemotaxis in Ca 2+ gradients generated in vitro, which has led to the hypothesis that Ca 2+ gradients in combination with gradients of the monocyte chemoattractant protein (MCP-1) regulate GnRH neuron migration during development Bandyopadhyay et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

“…Morris and coworkers (Morris and Chan, 2007) demonstrated that keratinocytes undergo chemotaxis in a Ca 2+ gradient in vitro and proposed that, in vivo, calcium and epidermal growth factor (EGF) might function together to promote wound healing, both presumably through chemotaxis. Osteoblasts have been shown to undergo chemotaxis in Ca 2+ gradients in vitro as well as in platelet-derived growth factor (PDGF) gradients in vitro (Sugimoto et al, 1993;Godwin and Soltoff, 1997), and monocytes have been shown to undergo chemotaxis in Ca 2+ as well as in chemokine gradients in vitro (Olszak et al, 2000). In addition, macrophages and macrophage-derived foam cells, which are involved in generating atherosclerotic lesions (Shi et al, 1996), and prostate and breast cancer cells also undergo chemotaxis in spatial gradients of Ca 2+ in vitro (Liao et al, 2006;Saidak et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Ca2+ chemotaxis inDictyostelium discoideum

Scherer

Kuhl

Wessels

et al. 2010

Journal of Cell Science

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SummaryUsing a newly developed microfluidic chamber, we have demonstrated in vitro that Ca 2+ functions as a chemoattractant of aggregationcompetent Dictyostelium discoideum amoebae, that parallel spatial gradients of cAMP and Ca 2+ are more effective than either alone, and that cAMP functions as a stronger chemoattractant than Ca 2+ . Effective Ca 2+ gradients are extremely steep compared with effective cAMP gradients. This presents a paradox because there is no indication to date that steep Ca 2+ gradients are generated in aggregation territories. However, given that Ca 2+ chemotaxis is co-acquired with cAMP chemotaxis during development, we speculate on the role that Ca 2+ chemotaxis might have and the possibility that steep, transient Ca 2+ gradients are generated during natural aggregation in the interstitial regions between cells.

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Extracellular calcium elicits a chemokinetic response from monocytes in vitro and in vivo

Cited by 138 publications

References 28 publications

The Calcium-Sensing Receptor as a Regulator of Cellular Fate in Normal and Pathological Conditions

The Calcium-Sensing Receptor as a Regulator of Cellular Fate in Normal and Pathological Conditions

Vitamin D and calcium insufficiency-related chronic diseases: molecular and cellular pathophysiology

Ca2+ chemotaxis inDictyostelium discoideum

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