Mechanisms of calcium disposal from osteoclastic resorption hemivacuole

Datta, HK; Horrocks, Ben

doi:10.1677/joe.0.1760001

Cited by 19 publications

(11 citation statements)

References 26 publications

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“…Since it is widely accepted that interstitial pH in bone is ∼7.1 [4], it is clear that one cannot extrapolate measurements carried out in the reabsorption lacunae to the bone interstitium. Furthermore, the Ca 2+ o released in this environment does not flood the osteoclasts, but it is reabsorbed by the osteoclasts via Ca 2+ channels and released out of the cell via the non-resorbing (basolateral) membrane, and also by non-specific bulk transport, via transcytosis [35]. Indeed, Berger and colleagues [9] have shown that, under steady-state conditions, a resorbing osteoclast releases no more than 2 mM Ca 2+ via the non-resorbing, basolateral membrane, a value which is fully compatible with the sensitivity range of activation for CaR and that we have shown to regulate directly many aspects of osteoblast function through this receptor.…”

Section: Car In Bonementioning

confidence: 99%

Novel regulatory aspects of the extracellular Ca2+-sensing receptor, CaR

Riccardi

Finney

Wilkinson

et al. 2009

Pflugers Arch - Eur J Physiol

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The capacity to sense and adapt to changes in environmental cues is of paramount importance for every living organism. From yeast to man, cells must be able to match cellular activities to growth environment and nutrient availability. Key to this process is the development of membrane-bound systems that can detect modifications in the extracellular environment and to translate these into biological responses. Evidence gathered over the last 15 years has demonstrated that many of these cell surface "sensors" belong to the G protein-coupled receptor superfamily. Crucial to our understanding of nutrient sensing in mammalian species has been the identification of the extracellular Ca(2+)/cation-sensing receptor, CaR. CaR was the first ion-sensing molecule identified in man and genetic studies in humans have revealed the importance of the CaR in mineral ion metabolism. Latter, it has become apparent that the CaR also plays an important role outside the Ca(2+) homeostatic system, as an integrator of multiple environmental signals for the regulation of many vital cellular processes, from cell-to-cell communication to secretion and cell survival/cell death. Recently, novel aspects of receptor function reveal an unexpected role for the CaR in the regulation of growth and development in utero.

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Section: Car In Bonementioning

confidence: 99%

Novel regulatory aspects of the extracellular Ca2+-sensing receptor, CaR

Riccardi

Finney

Wilkinson

et al. 2009

Pflugers Arch - Eur J Physiol

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“…Vesicular transcytosis is important in bone-resorbing osteoclasts. In contrast, during bone resorption, a large amount of Ca 2ϩ (up to 40 mM) and P i ion is generated within the osteoclast hemivacuole (10). The precise mechanisms involved in the disposal of Ca 2ϩ and P i are not clear.…”

mentioning

confidence: 99%

Unique uptake and efflux systems of inorganic phosphate in osteoclast-like cells

Ito

Haito²,

Furumoto³

et al. 2007

American Journal of Physiology-Cell Physiology

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During bone resorption, a large amount of inorganic phosphate (P(i)) is generated within the osteoclast hemivacuole. The mechanisms involved in the disposal of this P(i) are not clear. In the present study, we investigated the efflux of P(i) from osteoclast-like cells. P(i) efflux was activated by acidic conditions in osteoclast-like cells derived by the treatment of RAW264.7 cells with receptor activator of nuclear factor-kappaB ligand. Acid-induced P(i) influx was not observed in renal proximal tubule-like opossum kidney cells, osteoblast-like MC3T3-E1 cells, or untreated RAW264.7 cells. Furthermore, P(i) efflux was stimulated by extracellular P(i) and several P(i) analogs [phosphonoformic acid (PFA), phosphonoacetic acid, arsenate, and pyrophosphate]. P(i) efflux was time dependent, with 50% released into the medium after 10 min. The efflux of P(i) was increased by various inhibitors that block P(i) uptake, and extracellular P(i) did not affect the transport of [(14)C]PFA into the osteoclast-like cells. Preloading of cells with P(i) did not stimulate P(i) efflux by PFA, indicating that the effect of P(i) was not due to transstimulation of P(i) transport. P(i) uptake was also enhanced under acidic conditions. Agents that prevent increases in cytosolic free Ca(2+) concentration, including acetoxymethyl ester of 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, 2-aminoethoxydiphenyl borate, and bongkrekic acid, significantly inhibited P(i) uptake in the osteoclast-like cells, suggesting that P(i) uptake is regulated by Ca(2+) signaling in the endoplasmic reticulum and mitochondria of osteoclast-like cells. These results suggest that osteoclast-like cells have a unique P(i) uptake/efflux system and can prevent P(i) accumulation within osteoclast hemivacuoles.

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“…Guan et al [13] reported that when incubated with vascular smooth muscle cells, icariin blocked calcium channels that are either ligand- There are different viewpoints about the consequence of change in [Ca 2+ ] i in osteoclasts. Calcitonin, IL-4 and protein tyrosine kinase (PTK) inhibitors suppress osteoclast activity via acutely increasing the [Ca 2+ ] i , suggesting that elevation of [Ca 2+ ] i plays an inhibitory role in osteoclast function [14] . However, Berger et al [15] argue that an increase in [Ca 2+ ] i may be associated with activation, inhibition, or may have no effect on bone resorption.…”

Section: Discussionmentioning

confidence: 99%

Icariin suppresses bone resorption activity of rabbit osteoclasts in vitro

Huang

Zhang

et al. 2007

CHINESE SCI BULL

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The effect of icariin on the bone resorption activity of rabbit osteoclasts is assessed in vitro. Osteoclasts were isolated from Japanese white rabbits and cultured on plates with a sterilized bone slice in each well. After treatment with icariin at various concentrations, the bone resorption activity of osteoclasts was evaluated by examining pit areas, superoxide anion (generation, size and number of actin rings and intracellular calcium concentration [Ca 2+ ] i . As revealed by these data, icariin elicited continuous decline of [Ca 2+ ] i , making actin ring constricted and · O 2 -generation decreased. These events resulted in smaller and fewer pits which indicate suppressed bone resorption activity of rabbit osteoclasts by icariin. icariin, osteoclasts, actin ring, intracellular calcium, superoxideOsteoporosis is one of the leading causes of morbidity in the elderly. Bone loss in osteoporosis is caused by the excess of osteoclastic bone resorption over osteoblastic bone formation. Therefore, specific suppressers of osteoclast function and stimulators of bone formation are therapeutically promising in the treatment of osteoporosis. While a number of therapies are currently available (calcium supplements, vitamin D, fluoride, bisphosphonates, etc.), most are associated with disadvantages and some with deleterious side effects such as increased risks of thromboembolism or cancer [1][2][3] . In recent years, more and more researchers are turning their attention to phytochemicals. Daidzein and genistein, both are isoflavones from soybeans, and have been proved effective in the treatment of osteoporosis [4] . Icariin (C 33 H 40 O 15 ; molecular weight: 676.67) is a flavonoid glycoside isolated from Herba Epimedii (HEP) [5] , a medicinal herb traditionally used to treat fractures, bone and joint diseases, and gonad dysfunctions [6] . HEP extract, either as a single herbal extract or in a composite formula, could reduce the occurrence of osteoporosis in various experimental models [7][8][9][10][11] . However, few studies have been focused on the effect of pure icariin on cultured osteoclastic cells. The present study was designed to examine whether icariin can produce anti-resorption activity in vitro using rat osteoclasts. After treatment with icariin at various concentrations, the bone resorption activity of osteoclasts was evaluated by examining pit areas, superoxide anion ( · O 2 − ) generation, size and number of actin rings and intracellular calcium concentration [Ca 2+ ] i . Based on these data, an interpretation of the regulatory effect of icariin was proposed.

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Mechanisms of calcium disposal from osteoclastic resorption hemivacuole

Cited by 19 publications

References 26 publications

Novel regulatory aspects of the extracellular Ca2+-sensing receptor, CaR

Novel regulatory aspects of the extracellular Ca2+-sensing receptor, CaR

Unique uptake and efflux systems of inorganic phosphate in osteoclast-like cells

Icariin suppresses bone resorption activity of rabbit osteoclasts in vitro

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