The Purinergic Receptor P2X5 Regulates Inflammasome Activity and Hyper-multinucleation of Murine Osteoclasts

Overview

Journal Sci Rep

Specialty Science

Date 2017 Mar 17

PMID 28298636

Citations 35

Authors

Hyunsoo Kim

Matthew C Walsh

Noriko Takegahara

Sarah A Middleton

Hong-In Shin

Junhyong Kim

Yongwon Choi

Affiliations

Soon will be listed here.

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.

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