Promotion of osteoclast differentiation and activation in spite of impeded osteoblast-lineage differentiation under acidosis: Effects of acidosis on bone metabolism

Kato, Kohtaro; Morita, Ikuo

doi:10.5582/bst.2013.v7.1.33

Cited by 22 publications

(31 citation statements)

References 55 publications

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“…The increase in Ca 2+ concentration was more marked for β‐TCP (Figure a,b), which could be related to its higher solubility compared with CDHA. Additionally, an acidification of the cell culture medium, which is related to OC activity (Kato & Morita, ), was found for all CaP substrates in the presence of cells, compared with TCPS (Figure d). β‐TCP showed the highest pH variations, followed by CDHA‐H, which were maintained over the time points of the experiment.…”

Section: Discussionmentioning

confidence: 89%

Effect of calcium phosphate heparinization on the in vitro inflammatory response and osteoclastogenesis of human blood precursor cells

Díez-Escudero

Torreggiani

Pompo

et al. 2019

J Tissue Eng Regen Med

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The immobilization of natural molecules on synthetic bone grafts stands as a strategy to enhance their biological interactions. During the early stages of healing, immune cells and osteoclasts (OC) modulate the inflammatory response and resorb the biomaterial, respectively. In this study, heparin, a naturally occurring molecule in the bone extracellular matrix, was covalently immobilized on biomimetic calcium-deficient hydroxyapatite (CDHA). The effect of heparin-functionalized CDHA on inflammation and osteoclastogenesis was investigated using primary human cells and compared with pristine CDHA and beta-tricalcium phosphate (β-TCP). Biomimetic substrates led to lower oxidative stresses by neutrophils and monocytes than sintered β-TCP, even though no further reduction was induced by the presence of heparin. In contrast, heparinized CDHA fostered osteoclastogenesis. Optical images of stained TRAP positive cells showed an earlier and higher presence of multinucleated cells, compatible with OC at 14 days, while pristine CDHA and β-TCP present OC at 21-28 days. Although no statistically significant differences were found in the OC activity, microscopy images evidenced early stages of degradation on heparinized CDHA, compatible with osteoclastic resorption. Overall, the results suggest that the functionalization with heparin fostered the formation and activity of OC, thus offering a promising strategy to integrate biomaterials in the bone remodelling cycle by increasing their OC-mediated resorption.

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Section: Discussionmentioning

confidence: 89%

Effect of calcium phosphate heparinization on the in vitro inflammatory response and osteoclastogenesis of human blood precursor cells

Díez-Escudero

Torreggiani

Pompo

et al. 2019

J Tissue Eng Regen Med

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“…The molecular identity of the acid-inducible H + influx currents is presently unknown. The plasma membrane of osteoclasts express various acid-sensing cation channels (ASIC, TRP and HCN channels) [6,8,13,16,17] and acid-sensing anion channels (ClC7) [7]. However, these channels are unlikely to be responsible for the H + influx, as Na + and Cldid not affect the currents, although their contribution to the late currents remains to be resolved.…”

Section: Properties Of the Acid-inducible H + Influx Currentsmentioning

confidence: 99%

Acid-inducible proton influx currents in the plasma membrane of murine osteoclast-like cells

Kuno

Moriura

et al. 2016

Pflugers Arch - Eur J Physiol

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Acidification of the resorption pits, which is essential for dissolving bone, is produced by secretion of protons through vacuolar H(+)-ATPases in the plasma membrane of bone-resorbing cells, osteoclasts. Consequently, osteoclasts face highly acidic extracellular environments, where the pH gradient across the plasma membrane could generate a force driving protons into the cells. Proton influx mechanisms during the acid exposure are largely unknown, however. In this study, we investigated extracellular-acid-inducible proton influx currents in osteoclast-like cells derived from a macrophage cell line (RAW264). Decreasing extracellular pH to <5.5 induced non-ohmic inward currents. The reversal potentials depended on the pH gradients across the membrane and were independent of concentrations of Na(+), Cl(-), and HCO3 (-), suggesting that they were carried largely by protons. The acid-inducible proton influx currents were not inhibited by amiloride, a widely used blocker for cation channels/transporters, or by 4,4'-diisothiocyanato-2,2'-stilbenesulfonate(DIDS) which blocks anion channels/transporters. Additionally, the currents were not significantly affected by V-ATPase inhibitors, bafilomycin A1 and N,N'-dicyclohexylcarbodiimide. Extracellular Ca(2+) (10 mM) did not affect the currents, but 1 mM ZnCl2 decreased the currents partially. The intracellular pH in the vicinity of the plasma membrane was dropped by the acid-inducible H(+) influx currents, which caused overshoot of the voltage-gated H(+) channels after removal of acids. The H(+) influx currents were smaller in undifferentiated, mononuclear RAW cells and were negligible in COS7 cells. These data suggest that the acid-inducible H(+) influx (H(+) leak) pathway may be an additional mechanism modifying the pH environments of osteoclasts upon exposure to strong acids.

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“…These effects compromise bone mineralization. 3 The molecular mechanisms underlying the extracellular, acidic pHinduced actions in various tissues are not yet understood. Several protonsensing pathways have been identified in the last decade.…”

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confidence: 99%

“…Several protonsensing pathways have been identified in the last decade. [3][4][5] The protonsensing ionotropic receptors include transient receptor potential vanilloid-1 (TRPV1), acid-sensing ion channels, and a family of proton-sensing G-protein receptors, which includes ovarian cancer G protein-coupled receptor 1 (OGR1, also called GPR68). 6 OGR1 is expressed in osteoblasts, osteocytes, and osteoclasts.…”

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confidence: 99%

“…4 In osteoblasts, when this receptor is activated by high extracellular proton concentrations, it stimulates inositol trisphosphate formation and increases intracellular Ca 2þ concentration, which leads to an increase in cyclooxygenase (COX2) activity, and consequently enhanced synthesis of prostaglandin E2 (PGE2) and receptor activator of nuclear factor-kB ligand (RANKL), which in turn stimulates bone resorption by osteoclasts. 7 There is some inconsistency in the published reports about which proton sensors are expressed in osteoblasts, 3,5 or whether this leads to expression of RANKL. 7 It is also not clear what occurs after activation of the receptors on the osteoclasts, but the osteoclast is less prone to apoptosis during acidosis.…”

mentioning

confidence: 99%

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Role of proton receptor OGR1 in bone response to metabolic acidosis?

Jorgetti

Drüeke

Ott

2016

Kidney International

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Chronic metabolic acidosis stimulates bone resorption, resulting in loss of calcium and bicarbonate from bone. Both osteoblasts and osteoclasts sense extracellular H(+) by the G-protein coupled receptor, OGR1, whose activation leads to increased bone resorption as well as decreased bone formation. Krieger et al. examined the effect of OGR1 knockout in mice. They found an unexpected increase in bone resorption, but nevertheless an increase in bone volume linked to enhanced bone formation. This discovery opens a window of opportunity to explore potential new anabolic treatments for patients with low bone mass.

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Promotion of osteoclast differentiation and activation in spite of impeded osteoblast-lineage differentiation under acidosis: Effects of acidosis on bone metabolism

Cited by 22 publications

References 55 publications

Effect of calcium phosphate heparinization on the in vitro inflammatory response and osteoclastogenesis of human blood precursor cells

Effect of calcium phosphate heparinization on the in vitro inflammatory response and osteoclastogenesis of human blood precursor cells

Acid-inducible proton influx currents in the plasma membrane of murine osteoclast-like cells

Role of proton receptor OGR1 in bone response to metabolic acidosis?

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