Effects of Calcium on Gap Junctions Between Osteoblast-Like Cells in Culture

Schirrmacher, K.; Nonhoff, D.; Wiemann, Martin; Peterson-Grine, E.; Brink, Peter R.; Bingmann, D.

doi:10.1007/s002239900120

Cited by 33 publications

(25 citation statements)

References 28 publications

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“…When RBM cells were exposed to AGA, there was no significant effect on the Cx43 gene expression, but the Cx43 protein expression that mainly existed in osteoblasts significantly decreased. cAMP is one of the second messengers in the intracellular communication system and, in addition to calcium ions (29), plays a critical role in osteoblastic differentiation (12,14,21,27,28,31,34). These second messengers travel between adjacent cells directly through the gap junctions.…”

Section: Discussionmentioning

confidence: 99%

The function of connexin 43 on the differentiation of rat bone marrow cells in culture

Kamijo¹,

Haraguchi²,

Tonogi³

et al. 2006

Biomed. Res.

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Connexin (Cx) 43-mediated gap-junctional intercellular communication (GJC) mainly regulates the osteoblastic differentiation, but much of the function of Cx43 on the differentiation of bone marrow cells is unclear. This study is aimed to clarify relationship between the differentiation of rat bone marrow cells and the function of Cx43. Bone marrow cells derived from four-week-old Wistar strain rats were grown in the presence and absence of 18-α-glycyrrhetinic acid (AGA, 100 μM) to inhibit Cx43-mediated GJC. Expression of Cx43 gene and protein, and the level of intracellular cyclic adenosine monophosphate (cAMP) were determined as the assessment of the function in Cx43-mediated GJC, and alkaline phosphatase (ALP) activity and mineralization were measured as the assessment of osteoblastic differentiation. The Cx43 gene expression was first observed at 2 days, but under the condition in which rat bone marrow cells were treated with AGA, there was no significant effect on the Cx43 gene expression. By administrating AGA to rat bone marrow cells, all parameters of maturation but the Cx43 gene expression significantly decreased. The results of this experiment suggest that Cx43-mediated GJC plays a critical role in rat bone marrow cells, progress toward maturation.

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Section: Discussionmentioning

confidence: 99%

The function of connexin 43 on the differentiation of rat bone marrow cells in culture

Kamijo¹,

Haraguchi²,

Tonogi³

et al. 2006

Biomed. Res.

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“…Interestingly, this peptide also completely prevents the loss of femoral trabecular bone strength in ovariectomized rats. 17β-estradiol and 1,25(OH) 2 D 3 do not affect Cx43 expression in UMR106 cells (74), but somehow cause cell uncoupling in primary osteocytes (80,81). In contrast to PTH and PGE 2 , transforming growth factor β, osteogenin and bone morphogenetic protein-2 inhibit GJIC in MC3T3-E1 cells (82).…”

Section: Gap Junction Regulation By Hormones Growth Factors and Othementioning

confidence: 99%

“…However, in Cx45-predominantly expressed UMR106 cells, the propagation of Ca 2+ is mediated through gap junction-independent pathway, by which calcium waves are transmitted by activation of purinergic receptors, causing a release of intracellular calcium stores (92). In cultured primary osteoblasts and in bone marrow stromal cells, elevated intracellular Ca 2+ reduces intercellular coupling (72,81). Extracellular Ca 2+ influx through L-type Ca 2+ channels triggers the surge of intracellular Ca 2+ , which is transmitted via Cx43 gap junction channels (93).…”

Section: Gap Junctions In Ca 2+ Signaling and Propagation In Bone Cellsmentioning

confidence: 99%

Roles of gap junctions and hemichannels in bone cell functions and in signal transmission of mechanical stress

Jiang¹,

2007

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Gap junctions formed by connexins (Cx) play an important role in transmitting signals between bone cells such as osteoblasts and osteoclasts, cells responsible for bone formation and bone remodeling, respectively. Gap junction intercellular communication (GJIC) has been demonstrated to mediate the process of osteoblast differentiation and bone formation. Furthermore, GJIC propagates Ca 2+ signaling, conveys anabolic effects of hormones and growth factors, and regulates gene transcription of osteoblast differentiation markers. GJIC is also implicated to regulate osteoclast formation, survival and apoptosis. Compared with other bone cells, the most abundant type are osteocytes, which express large amounts of connexins. Mechanosensing osteocytes connect and form gap junctions with themselves and other cells only through the tips of their dendritic processes, a relatively small percent of the total cell surface area compared to other cells. Recent studies show that in addition to gap junctions, osteoblasts and osteocytes express functional hemichannels, the un-opposed halves of gap junction channels. Hemichannels are localized at the cell surface and function independently of gap junctions. Hemichannels in osteocytes mediate the immediate release of prostaglandins in response to mechanical stress. The major challenges remaining in the field are how the functions of these two types of channels are coordinated in bone cells and what the asserted, distinct effects of these channels are on bone formation and remodeling processes, and on conveying signals elicited by mechanical loading. KeywordsBone; Gap Junctions; Hemichannels; Cx43; Connexin; Osteoblast; Osteocyte; Mechanical Stress; Review INTRODUCTION Gap Junctions in Bone CellsGap junctions are transmembrane channels, which connect the cytoplasm of adjacent cells. These channels permit molecules with molecular weights approximately less than 1 kD a such as small metabolites, ions, and intracellular signaling molecules (i.e. calcium, cAMP, inositol triphosphate) to pass through. Gap junction channels have been demonstrated to be important in modulating cell signaling and tissue function in many organs, such as heart, liver, peripheral nerve, ovary, ear and lens of the eye (1-8). Gap junctions are formed by members of a family of sequentially and structurally related proteins known as connexins. Approximately twenty connexins have been identified and cloned from various tissues and cells (9-11). Six monomers of connexins are joined head-to-head across the extracellular "gap" between two adjacent cells (21,26,27). However, we found that Cx45 protein is expressed in bone marrow, but not in osteoblasts, osteocytes and osteoclasts in the alveolar bone tissues of the tooth (28).Functional gap junctions in osteoblasts were first demonstrated with electrical conductance and dye injection (29). Voltage-sensitive gap junction currents were detected in osteoblastic cells derived from calvarias of new-born rats with a single gap junction channel conductance of approxim...

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“…How these local [Ca 2ϩ ] i signals affect gap junctions, though, is unclear. Because Ca 2ϩ has previously been shown to reduce permeability of gap junctions formed by Cx43 (48,50), a direct effect of Ca 2ϩ is possible but an involvement of other Ca 2ϩ -sensitive messengers cannot be excluded (36).…”

Section: Downregulation Of ␣ 2 Isoform Inhibits Intercellular Communimentioning

confidence: 99%

The α₂ isoform of the Na,K-pump is important for intercellular communication, agonist-induced contraction, and EDHF-like response in rat mesenteric arteries

Matchkov

Moeller-Nielsen

Dam

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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Matchkov VV, Moeller-Nielsen N, Dam VS, Nourian Z, Boedtkjer DM, Aalkjaer C. The ␣2 isoform of the Na,K-pump is important for intercellular communication, agonist-induced contraction, and EDHF-like response in rat mesenteric arteries. Am J Physiol Heart Circ Physiol 303: H36 -H46, 2012. First published May 4, 2012 doi:10.1152/ajpheart.00673.2011The specific role of different isoforms of the Na,K-pump in the vascular wall is still under debate. We have previously suggested that the ␣2 isoform of the Na,K-pump (␣2), Na ϩ , Ca 2ϩ -exchange (NCX), and connexin43 form a regulatory microdomain in smooth muscle cells (SMCs), which controls intercellular communication and contractile properties of the vascular wall. We have tested this hypothesis by downregulating ␣2 in cultured SMCs and in small arteries with siRNA in vivo. Intercellular communication was assessed by using membrane capacitance measurements. Arteries transfected in vivo were tested for isometric and isobaric force development in vitro; [Ca 2ϩ ]i was measured simultaneously. Cultured rat SMCs were well-coupled electrically, but 10 M ouabain uncoupled them. Downregulation of ␣ 2 reduced electrical coupling between SMCs and made them insensitive to ouabain. Downregulation of ␣2 in small arteries was accompanied with significant reduction in NCX expression. Acetylcholine-induced relaxation was not different between the groups, but the endotheliumdependent hyperpolarizing factor-like component of the response was significantly diminished in ␣2-downregulated arteries. Micromolar ouabain reduced in a concentration-dependent manner the amplitude of norepinephrine (NE)-induced vasomotion. Sixty percent of the ␣ 2-downregulated arteries did not have vasomotion, and vasomotion in the remaining 40% was ouabain insensitive. Although ouabain increased the sensitivity to NE in the control arteries, it had no effect on ␣ 2-downregulated arteries. In the presence of a low NE concentration the ␣ 2-downregulated arteries had higher [Ca 2ϩ ]i and tone. However, the NE EC50 was reduced under isometric conditions, and maximal contraction was reduced under isometric and isobaric conditions. The latter was caused by a reduced Ca 2ϩ -sensitivity. The ␣2-downregulated arteries also had reduced contraction to vasopressin, whereas the contractile response to high K ϩ was not affected. Our results demonstrate the importance of ␣ 2 for intercellular coupling in the vascular wall and its involvement in the regulation of vascular tone. Na ϩ , Ca 2ϩ exchanger; smooth muscle cell synchronization; short interfering RNA; norepinephrine contractility; endothelium-dependent hyperpolarizing factor THE ELECTROGENIC NA,K-PUMP modifies numerous cellular pathways by modulating Na ϩ -coupled transport. The functional significance of the Na,K-pump is dependent upon the isoform. The catalytic ␣-subunit exists in three isoforms (5). These isoforms have different affinities for cardiac glycosides, kinetics, and regulation but show high structural homology and are difficult to distinguish at a fu...

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Effects of Calcium on Gap Junctions Between Osteoblast-Like Cells in Culture

Cited by 33 publications

References 28 publications

The function of connexin 43 on the differentiation of rat bone marrow cells in culture

The function of connexin 43 on the differentiation of rat bone marrow cells in culture

Roles of gap junctions and hemichannels in bone cell functions and in signal transmission of mechanical stress

The α₂ isoform of the Na,K-pump is important for intercellular communication, agonist-induced contraction, and EDHF-like response in rat mesenteric arteries

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Effects of Calcium on Gap Junctions Between Osteoblast-Like Cells in Culture

Cited by 33 publications

References 28 publications

The function of connexin 43 on the differentiation of rat bone marrow cells in culture

The function of connexin 43 on the differentiation of rat bone marrow cells in culture

Roles of gap junctions and hemichannels in bone cell functions and in signal transmission of mechanical stress

The α2 isoform of the Na,K-pump is important for intercellular communication, agonist-induced contraction, and EDHF-like response in rat mesenteric arteries

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The α₂ isoform of the Na,K-pump is important for intercellular communication, agonist-induced contraction, and EDHF-like response in rat mesenteric arteries