Intracellular and Extracellular ATP Coordinately Regulate the Inverse Correlation between Osteoclast Survival and Bone Resorption

Miyazaki, Tsuyoshi; Iwasawa, Masaki; Nakashima, Tomoki; Mori, Shuuichi; Shigemoto, Kazuhiro; Nakamura, Hiroaki; Katagiri, Hideki; Takayanagi, Hiroshi; Tanaka, Sakae

doi:10.1074/jbc.m112.385369

Cited by 107 publications

(98 citation statements)

References 66 publications

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“…Extracellular ATP levels control and modulate the activity of both the osteoblasts (Orriss et al, 2013) and the osteoclasts (Miyazaki et al, 2012), implying that the nucleotides released by osteoblasts in bone could locally affect mineralization. By contrast, in vitro through special transporters, e.g.…”

Section: Discussionmentioning

confidence: 99%

Amorphous Ca2+ polyphosphate nanoparticles regulate the ATP level in bone-like SaOS-2 cells

Müller

Tolba

Feng

et al. 2015

Journal of Cell Science

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Polyphosphate ( polyP) is a physiologically occurring polyanion that is synthesized especially in bone-forming osteoblast cells and blood platelets. We used amorphous polyP nanoparticles, complexed with Ca 2+ , that have a globular size of ∼100 nm. Because polyP comprises inorganic orthophosphate units that are linked together through highenergy phosphoanhydride bonds, we questioned whether the observed morphogenetic effect, elicited by polyP, is correlated with the energy-generating machinery within the cells. We show that exposure of SaOS-2 osteoblast-like cells to polyP results in a strong accumulation of mitochondria and a parallel translocation of the polyP-degrading enzyme alkaline phosphatase to the cell surface. If SaOS-2 cells are activated by the mineralization activation cocktail (comprising β-glycerophosphate, ascorbic acid and dexamethasone) and additionally incubated with polyP, a tenfold intracellular increase of the ATP level occurs. Even more, in those cells, an intensified release of ATP into the extracellular space is also seen. We propose and conclude that polyP acts as metabolic fuel after the hydrolytic cleavage of the phosphoanhydride linkages, which contributes to hydroxyapatite formation on the plasma membranes of osteoblasts.

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Section: Discussionmentioning

confidence: 99%

Amorphous Ca2+ polyphosphate nanoparticles regulate the ATP level in bone-like SaOS-2 cells

Müller

Tolba

Feng

et al. 2015

Journal of Cell Science

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“…4,35 The released ATP negatively regulated bone-resorbing activity through an autocrine/paracrine feedback loop. 21,30 When the extracellular ATP was hydrolyzed by nucleotidase apyrase, the micropipette indentationinduced elevation of [Ca 2+ l i didn't change, indicating that nucleotide release is not essential for mechanically induced Ca 2+ influx. 42 We blocked the binding of ATP to the purinergic receptor with suramin and found that responsive percentage of osteoclasts decreased at low FSS level while almost all of cells responded for high FSS level (Fig.…”

Section: Discussionmentioning

confidence: 99%

Fluid Flow-Induced Calcium Response in Osteoclasts: Signaling Pathways

Liu

et al. 2014

Ann Biomed Eng

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Abstract-Intracellular calcium oscillation and its downstream signaling in osteoclasts is believed to play critical roles in regulating bone resorption. Our previous study demonstrated that fluid shear stress (FSS) induced more calcium responsive peaks in the late differentiated osteoclasts than the early ones. In this paper, the signaling pathways of FSS-induced calcium response for the osteoclasts in different differentiation stages were studied. RAW264.7 macrophage cells were induced to differentiate into osteoclasts with the conditioned medium from MC3T3-E1 osteoblasts. Furthermore pharmacological agents were added to block the specific signaling pathways. Finally the cells were exposed to FSS at different levels (1 or 10 dyne/cm 2 ) after being induced for 4 or 8 days. The results showed that the mechanosensitive, cation-selective channels, phospholipase C (PLC) and endoplasmic reticulum constituted the major signaling pathway for mechanical stimulation-induced calcium response in osteoclasts. Extracellular calcium or ATP involved with calcium oscillation in a FSS magnitude-dependent manner. This pathway study may help to give insight into the molecular mechanism of mechanical stimulation-regulated bone remodeling.

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“…However, recent studies suggest that components of ATP synthase are also present on the outer surface of the plasma membrane, where they function as receptors for various ligands and are known to be involved in lipid formation, the regulation of endothelial cell proliferation and differentiation, and immune responses in tumor cells (82)(83)(84)(85). It is also known that intracellular ATP levels regulate the inverse correlation between osteoclast survival and bone resorption through an unknown mechanism, and that extracellular ATP likely exerts inhibitory effects on osteoclast survival and the bone remodeling and resorption induced by mature osteoclasts through the alteration of cytoskeletal structures (86).…”

Section: Discussionmentioning

confidence: 99%

Proteomic Analysis of Gingival Tissue and Alveolar Bone during Alveolar Bone Healing

Yang

Kwon

Kook

et al. 2013

Molecular & Cellular Proteomics

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Bone tissue regeneration is orchestrated by the surrounding supporting tissues and involves the build-up of osteogenic cells, which orchestrate remodeling/healing through the expression of numerous mediators and signaling molecules. Periodontal regeneration models have proven useful for studying the interaction and communication between alveolar bone and supporting soft tissue. We applied a quantitative proteomic approach to analyze and compare proteins with altered expression in gingival soft tissue and alveolar bone following tooth extraction. For target identification and validation, hard and soft tissue were extracted from mini-pigs at the indicated times after tooth extraction. From triplicate experiments, 56 proteins in soft tissue and 27 proteins in alveolar bone were found to be differentially expressed before and after tooth extraction. The expression of 21 of those proteins was altered in both soft tissue and bone. Comparison of the activated networks in soft tissue and alveolar bone highlighted their distinct responsibilities in bone and tissue healing. Moreover, we found that there is crosstalk between identified proteins in soft tissue and alveolar bone with respect to cellular assembly, organization, and communication. Among these proteins, we examined in detail the expression patterns and associated networks of ATP5B and fibronectin 1. ATP5B is involved in nucleic acid metabolism, small molecule biochemistry, and neurological disease, and fibronectin 1 is involved in cellular assembly, organization, and maintenance. Collectively, our findings indicate that bone regeneration is accompanied by a profound interaction among networks regulating cellular resources, and they provide novel insight into the molecular mechanisms involved in the healing of periodontal tissue after tooth extraction. Molecular & Cellular Proteomics

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Intracellular and Extracellular ATP Coordinately Regulate the Inverse Correlation between Osteoclast Survival and Bone Resorption

Cited by 107 publications

References 66 publications

Amorphous Ca2+ polyphosphate nanoparticles regulate the ATP level in bone-like SaOS-2 cells

Amorphous Ca2+ polyphosphate nanoparticles regulate the ATP level in bone-like SaOS-2 cells

Fluid Flow-Induced Calcium Response in Osteoclasts: Signaling Pathways

Proteomic Analysis of Gingival Tissue and Alveolar Bone during Alveolar Bone Healing

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