Ion channels and transporters in osteoclasts

Supanchart, Chayarop; Kornak, Uwe

doi:10.1016/j.abb.2008.03.029

Cited by 40 publications

(33 citation statements)

References 73 publications

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“…The secretion of protons into the resorption lacuna generates an intracellular acid deficit. A basolateral HCO 3 Ϫ /Cl Ϫ anion exchanger regulates intracellular pH through the efflux of excess bicarbonate (4,8). Until this study, the genetic identity of this exchanger was unknown.…”

Section: Discussionmentioning

confidence: 99%

“…A HCO 3 Ϫ / Cl Ϫ anion exchanger in the basolateral membrane prevents cytoplasmic alkalinization by providing egress for excess base. Accordingly, anion exchange inhibitors repress the bone resorbing activity of osteoclasts, and incubation of active osteoclasts in Cl Ϫ -free media results in an increase in cytoplasmic pH (4,(6)(7)(8). Despite these data, the genetic identity of the basolateral HCO 3 Ϫ /Cl Ϫ anion exchanger in osteoclasts, and its role in bone remodeling in vivo, has not been described.…”

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confidence: 89%

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HCO ₃ ⁻ /Cl ⁻ anion exchanger SLC4A2 is required for proper osteoclast differentiation and function

Glimcher

Aliprantis

2008

Proc. Natl. Acad. Sci. U.S.A.

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As the only cell capable of bone resorption, the osteoclast is a central mediator of skeletal homeostasis and disease. To efficiently degrade mineralized tissue, these multinucleated giant cells secrete acid into a resorption lacuna formed between their apical membrane and the bone surface. For each proton pumped into this extracellular compartment, one bicarbonate ion remains in the cytoplasm. To prevent alkalinization of the cytoplasm, a basolateral bicarbonate/chloride exchanger provides egress for intracellular bicarbonate. However, the identity of this exchanger is unknown. Here, we report that the bicarbonate/chloride exchanger, solute carrier family 4, anion exchanger, member 2 (SLC4A2), is up-regulated during osteoclast differentiation. Suppression of Slc4a2 expression by RNA interference inhibits the ability of RAW cells, a mouse macrophage cell line, to differentiate into osteoclasts and resorb mineralized matrix in vitro. Accordingly, Slc4a2-deficient mice fail to remodel the primary, cartilaginous skeletal anlagen. Abnormal multinucleated giant cells are present in the bone marrow of Slc4a2-deficient mice. Though these cells express the osteoclast markers CD68, cathepsin K, and NFATc1, compared with their wild-type (WT) counterparts they are larger, fail to express tartrate-resistant acid phosphatase (TRAP) activity, and display a propensity to undergo apoptosis. In vitro Slc4a2-deficient osteoclasts are unable to resorb mineralized tissue and cannot form an acidified, extracellular resorption compartment. These data highlight SLC4A2 as a critical mediator of osteoclast differentiation and function in vitro and in vivo.one is a remarkable biomaterial composed of organic and inorganic molecules that remodels to preserve structural integrity and adapt to stress. Two cells execute this process: the osteoblast and osteoclast, which synthesize and catabolize bone respectively. An imbalance between osteoclast and osteoblast activity perturbs bone quality, leading to fractures or skeletal deformities (1, 2).The osteoclast is a multinucleated giant cell that differentiates from myeloid precursors under the influence of the osteoblastderived cytokines, macrophage-colony stimulating factor (MCSF) and receptor activator for nuclear factor-B ligand (RANKL). This process is controlled by the transcription factor, nuclear factor of activated T cells c1 (NFATc1), which is induced by RANKL and governs the expression of genes necessary for osteoclast formation and function (3). After differentiation, the osteoclast polarizes, forming a resorption lacuna between its apical membrane and the mineralized bone surface. Within this space, the osteoclast secretes enzymes, as well as acid, via an apical, H ϩ -vacuolar ATPase. The low pH of the resorption lacuna activates these proteolytic enzymes and promotes dissolution of crystalline calcium phosphate. To maintain electroneutrality, a parallel chloride/proton antiporter releases a chloride ion with each proton (4). In humans and mice, mutations in either the proton pump (T...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 89%

HCO ₃ ⁻ /Cl ⁻ anion exchanger SLC4A2 is required for proper osteoclast differentiation and function

Glimcher

Aliprantis

2008

Proc. Natl. Acad. Sci. U.S.A.

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“…Transient increases in intracellular calcium are common initiators of signaling cascades, survival signals, and enzyme activation (1). Many extracellular signals modify the intracellular concentration of Ca 2ϩ ([Ca 2ϩ ] i ) in osteoclasts and, by doing so, modulate their functions (2).…”

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confidence: 99%

TRPV-5 Mediates a Receptor Activator of NF-κB (RANK) Ligand-induced Increase in Cytosolic Ca2+ in Human Osteoclasts and Down-regulates Bone Resorption

Chamoux

Bisson

Payet

et al. 2010

Journal of Biological Chemistry

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“…The membrane facing the vascular compartment is instead called ''basolateral membrane'' [1] (Fig. 1C) and presents with important asymmetric distribution of ion transporters [5]. This led to the definition of the osteoclast as an ''epithelial-like cell'', with an apical membrane facing the bone and a basolateral membrane facing the vascular stream [1] (Fig.…”

Section: Osteoclast Morphology and Resorptive Structuresmentioning

confidence: 98%

Reprint of: The Great Beauty of the osteoclast

Cappariello

Maurizi

Veeriah

et al. 2014

Archives of Biochemistry and Biophysics

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Ion channels and transporters in osteoclasts

Cited by 40 publications

References 73 publications

HCO ₃ ⁻ /Cl ⁻ anion exchanger SLC4A2 is required for proper osteoclast differentiation and function

HCO ₃ ⁻ /Cl ⁻ anion exchanger SLC4A2 is required for proper osteoclast differentiation and function

TRPV-5 Mediates a Receptor Activator of NF-κB (RANK) Ligand-induced Increase in Cytosolic Ca2+ in Human Osteoclasts and Down-regulates Bone Resorption

Reprint of: The Great Beauty of the osteoclast

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Ion channels and transporters in osteoclasts

Cited by 40 publications

References 73 publications

HCO 3 − /Cl − anion exchanger SLC4A2 is required for proper osteoclast differentiation and function

HCO 3 − /Cl − anion exchanger SLC4A2 is required for proper osteoclast differentiation and function

TRPV-5 Mediates a Receptor Activator of NF-κB (RANK) Ligand-induced Increase in Cytosolic Ca2+ in Human Osteoclasts and Down-regulates Bone Resorption

Reprint of: The Great Beauty of the osteoclast

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HCO ₃ ⁻ /Cl ⁻ anion exchanger SLC4A2 is required for proper osteoclast differentiation and function

HCO ₃ ⁻ /Cl ⁻ anion exchanger SLC4A2 is required for proper osteoclast differentiation and function