Lysophosphatidic acid stimulates osteoclast fusion through OC-STAMP and P2X7 receptor signaling

Hwang, Young Sun; Taek, Gwang; Park, Kwang Kyun; Chung, Won Yoon

doi:10.1007/s00774-013-0470-9

Cited by 18 publications

(11 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Phosphatidic acid, LPA and DAG are involved in many membrane fusion and membrane fission events, such as fission of Golgi membranes , fission during endocytic transport , vacuole fission and fusion , mitochondrial dynamics , exocytosis , vesicle‐vesicle fusion , myoblast fusion , osteoclast fusion , membrane fusion during sporulation , membrane fusion during fertilization . Fusion of PA‐containing vesicles was studied in Refs .…”

Section: The Role Of Pa In Membrane Fusion and Membrane Fissionmentioning

confidence: 99%

“…Phosphatidic acid, LPA and DAG are involved in many membrane fusion and membrane fission events, such as fission of Golgi membranes [140,162,163,[165][166][167][168][169], fission during endocytic transport [170,171], vacuole fission [172] and fusion [132,147,[173][174][175], mitochondrial dynamics [17,40,95,[176][177][178][179][180][181][182][183][184][185], exocytosis [30,40,76,79,125,[186][187][188][189][190][191][192][193][194], vesicle-vesicle fusion [164], myoblast fusion [195,196], osteoclast fusion [197], membrane fusion during sporulation [198][199][200][201], membrane fusion during fertilization [202,203]. Fusion of PA-containing vesicles was studied in Refs [87,…”

Section: The Role Of Pa In Membrane Fusion and Membrane Fissionmentioning

confidence: 99%

See 1 more Smart Citation

Phosphatidic acid in membrane rearrangements

et al. 2019

View full text Add to dashboard Cite

Phosphatidic acid (PA) is the simplest cellular glycerophospholipid characterized by unique biophysical properties: a small headgroup; negative charge; and a phosphomonoester group. Upon interaction with lysine or arginine, PA charge increases from −1 to −2 and this change stabilizes protein–lipid interactions. The biochemical properties of PA also allow interactions with lipids in several subcellular compartments. Based on this feature, PA is involved in the regulation and amplification of many cellular signalling pathways and functions, as well as in membrane rearrangements. Thereby, PA can influence membrane fusion and fission through four main mechanisms: it is a substrate for enzymes producing lipids (lysophosphatidic acid and diacylglycerol) that are involved in fission or fusion; it contributes to membrane rearrangements by generating negative membrane curvature; it interacts with proteins required for membrane fusion and fission; and it activates enzymes whose products are involved in membrane rearrangements. Here, we discuss the biophysical properties of PA in the context of the above four roles of PA in membrane fusion and fission.

show abstract

Section: The Role Of Pa In Membrane Fusion and Membrane Fissionmentioning

confidence: 99%

Section: The Role Of Pa In Membrane Fusion and Membrane Fissionmentioning

confidence: 99%

Phosphatidic acid in membrane rearrangements

et al. 2019

View full text Add to dashboard Cite

show abstract

“… 25 LPA also enhances differentiation of osteoclast precursors and regulates the morphology, resorptive activity, and survival of mature osteoclasts. 26 – 28 Therefore, LPA, LPA signaling, and LPA target molecules may be diagnostic and therapeutic targets to treat patients with prostate cancer.…”

Section: Discussionmentioning

confidence: 99%

Constitutive and Inducible Expression of Invasionrelated Factors in PC-3 Prostate Cancer Cells

Hwang

Lindholm

2015

J Cancer Prev

Self Cite

View full text Add to dashboard Cite

Background:Tumor growth and invasion are interconnected with the tumor microenvironment. Overexpression of genes that regulate cancer cell invasion by growth factors, cytokines, and lipid factors can affect cancer aggressiveness. A comparative gene expression analysis between highly invasive and low invasive cells revealed that various genes are differentially expressed in association with invasive potential. In this study, we selected variant PC-3 prostate cancer cell sublines and discovered critical molecules that contributed to their invasive potential.Methods:The high invasive and low invasive variant PC-3 cell sublines were obtained by serial selection following Matrigel-coated Transwell invasion and were characterized by Transwell invasion, luciferase reporter assay, and Rhotekin pull-down assay. Lysophosphatidic acid (LPA) was added to the cultures to observe the response to this extracellular stimulus. The essential molecules related with cancer invasiveness were detected with Northern blotting, quantitative reverse transcription-polymerase chain reaction, and cDNA microarray.Results:Highly invasive PC-3 cells showed higher nuclear factor kappa B (NF-κB), activator protein 1 (AP-1) and RhoA activities than of low invasive PC-3 cells. LPA promoted cancer invasion through NF-κB, AP-1, and RhoA activities. Thrombospondin-1, interleukin-8, kallikrein 6, matrix metalloproteinase-1, and tissue factor were overexpressed in the highly invasive PC-3 variant cells and further upregulated by LPA stimulation.Conclusions:The results suggest that the target molecules are involved in invasiveness of prostate cancer. These molecules may have clinical value for anti-invasion therapy by serving as biomarkers for the prediction of aggressive cancers and the detection of pharmacological inhibitors.

show abstract

“…Therefore, the authors speculate that ATP release via the P2X7R pore is needed for osteoclastic fusion, although the effect may be indirect involving other purinergic receptors. Since then, the role of P2X7R in driving LPA-stimulated osteoclast fusion has been highlighted (Hwang et al 2013). The authors showed that siRNA-induced P2X7R knockdown in RAW 264.7 cells downregulated the expression of osteoclastic functional makers including nuclear factor of activated T cells 1 (NFATc1), cathepsin K, tartrate-resistant acid phosphatase (TRAP), AT6v0d2, c-Src, c-Jun, and Car2, in addition to suppression of the LPA-stimulated increase in osteoclast Effect of P2X7R on osteoclastogenesis: extracellular ATP induces commitment of haematopoietic stem cells (HSCs) towards a more committed, myeloid progenitor/pre-osteoclast cell.…”

Section: Mature Cellsmentioning

confidence: 99%

P2X7 receptors: role in bone cell formation and function

Agrawal¹,

Gartland²

2015

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

The role of the P2X7 receptor (P2X7R) is being explored with intensive interest in the context of normal bone physiology, bone-related diseases and, to an extent, bone cancer. In this review, we cover the current understanding of P2X7R regulation of bone cell formation, function and survival. We will discuss how the P2X7R drives lineage commitment of undifferentiated bone cell progenitors, the vital role of P2X7R activation in bone mineralisation and its relatively unexplored role in osteocyte function. We also review how P2X7R activation is imperative for osteoclast formation and its role in bone resorption via orchestrating osteoclast apoptosis. Variations in the gene for the P2X7R (P2RX7) have implications for P2X7R-mediated processes and we review the relevance of these genetic variations in bone physiology. Finally, we highlight how targeting P2X7R may have therapeutic potential in bone disease and cancer. Purinergic signallingIn the last four decades, extensive investigations have led to the recognition of ATP from a 'molecular unit of energy' to an extracellular messenger molecule. ATP-sensitive purinoceptors, omnipresent in vertebrate tissues, are involved in a wide variety of physiological roles (Burnstock 2013) and their function has also been demonstrated in invertebrates (Verkhratsky & Burnstock 2014). While they traditionally act as cell surface sensors (Khakh & North 2006), their participation in signalling within the intracellular compartment in mammals (Qureshi et al. 2007, Kuehnel et al. 2009, Stokes & Surprenant 2009, Toulme et al. 2010) and even protozoans (Fountain et al. 2007, Ludlow et al. 2009, Sivaramakrishnan & Fountain 2012 has also been recognised.Purines (adenine, guanine and uridine) can act as signalling molecules in the form of their 5 0 -nucleotide triphosphates (such as ATP, GTP and UTP), diphosphates (ADP), monophosphate (AMP) or as a nucleoside (adenosine). They can activate one or more of the 19 receptors which are sorted into three classes: P1 (nucleoside) receptors; the metabotropic P2Y receptors and the ionotropic P2X, both of which are nucleotide triggered. Recently, a new family of purine receptors, AdeR or P0-receptors, responsive to adenine has been cloned from rodents (Bender et al. 2002, Gorzalka et al. 2005, von Kugelgen et al. 2008, Thimm et al. 2013, although the human homologue is yet to be identified. Structural and stoichiometrical evidence suggests that all P2X receptor (P2XR) subunits trimerise to form functional receptors (Nicke et al. 1998, Barrera et al. 2005, Mio et al. 2005, Kaczmarek-Hajek et al. 2012 with the subunits forming either homomultimers or heteromultimers depending on the subtypes (Burnstock 2007). Each unit comprises two transmembrane domains (TM1 and TM2) with an intervening large extracellular loop and cytoplasmic N-and C-termini, and the primary agonist of all homomeric and heteromeric P2XR is ATP. The current view holds that ligand binding causes reduction in the Journal of Molecular EndocrinologyReview A AGRAWAL and A GARTLAND P...

show abstract

Lysophosphatidic acid stimulates osteoclast fusion through OC-STAMP and P2X7 receptor signaling

Cited by 18 publications

References 44 publications

Phosphatidic acid in membrane rearrangements

Phosphatidic acid in membrane rearrangements

Constitutive and Inducible Expression of Invasionrelated Factors in PC-3 Prostate Cancer Cells

P2X7 receptors: role in bone cell formation and function

Contact Info

Product

Resources

About