title: The purinergic receptor P2X5 regulates inflammasome activity and hyper-multinucleation of murine osteoclasts.
abstract: Excessive bone resorption by osteoclasts (OCs) can result in serious clinical outcomes, including bone loss that may weaken skeletal or periodontal strength. Proper bone homeostasis and skeletal strength are maintained by balancing OC function with the bone-forming function of osteoblasts. Unfortunately, current treatments that broadly inhibit OC differentiation or function may also interfere with coupled bone formation. We therefore identified a factor, the purinergic receptor P2X5 that is highly expressed during the OC maturation phase, and which we show here plays no apparent role in early bone development and homeostasis, but which is required for osteoclast-mediated inflammatory bone loss and hyper-multinucleation of OCs. We further demonstrate that P2X5 is required for ATP-mediated inflammasome activation and IL-1β production by OCs, and that P2X5-deficient OC maturation is rescued in vitro by addition of exogenous IL-1β. These findings identify a mechanism by which OCs react to inflammatory stimuli, and may identify purinergic signaling as a therapeutic target for bone loss-related inflammatory conditions.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
authors.forename: Hyunsoo
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Walsh
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.|Next generation Optical Immune-imaging, WPI-Immunology Frontier Research Center, Osaka University, Suita, Osaka, 565-0871, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Takegahara
authors.affiliation: Department of Biology, Department of Computer and Information Science, School of Arts and Sciences, Program in Single Cell Biology, University of Pennsylvania, Philadelphia, PA, 19104, USA.
authors.forename: Sarah A
authors.identifier: 0000-0002-9504-2574
authors.initials: SA
authors.lastname: Middleton
authors.affiliation: IHBR, Department of Oral Pathology, School of Dentistry, Kyungpook National University, Daegu, 700412, South Korea.
authors.forename: Hong-In
authors.initials: HI
authors.lastname: Shin
authors.affiliation: Department of Biology, Department of Computer and Information Science, School of Arts and Sciences, Program in Single Cell Biology, University of Pennsylvania, Philadelphia, PA, 19104, USA.
authors.forename: Junhyong
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA. ychoi3@mail.med.upenn.edu.
authors.forename: Yongwon
authors.initials: Y
authors.lastname: Choi
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001846:Bone Development; D002454:Cell Differentiation; D002478:Cells, Cultured; D055785:Gene Knockdown Techniques; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000009:adverse effects; D051379:Mice; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D058485:Receptors, Purinergic P2X5 / Q000235:genetics / Q000378:metabolism*
chemical_list: C587672:IL1B protein, mouse; D058847:Inflammasomes; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; C546466:P2rx5 protein, mouse; D058485:Receptors, Purinergic P2X5; D000255:Adenosine Triphosphate