@article{fc6e0a97949243959967eb90b4be185c,
title = "Actions of the NLRP3 and NLRC4 inflammasomes overlap in bone resorption",
abstract = "Overwhelming evidence indicates that excessive stimulation of innate immune receptors of the NOD-like receptor (NLR) family causes significant damage to multiple tissues, yet the role of these proteins in bone metabolism is not well known. Here, we studied the interaction between the NLRP3 and NLRC4 inflammasomes in bone homeostasis and disease. We found that loss of NLRP3 or NLRC4 inflammasome attenuated osteoclast differentiation in vitro. At the tissue level, lack of NLRP3, or NLRC4 to a lesser extent, resulted in higher baseline bone mass compared to wild-type (WT) mice, and conferred protection against LPS-induced inflammatory osteolysis. Bone mass accrual in mutant mice correlated with lower serum IL-1β levels in vivo. Unexpectedly, the phenotype of Nlrp3-deficient mice was reversed upon loss of NLRC4 as bone mass was comparable between WT mice and Nlrp3;Nlrc4 knockout mice. Thus, although bone homeostasis is perturbed to various degrees by the lack of NLRP3 or NLRC4, this tissue appears to function normally upon compound loss of the inflammasomes assembled by these receptors.",
keywords = "IL-1β, NLRC4, NLRP3, bone, inflammasome, inflammation, osteoclast",
author = "Yael Alippe and Dustin Kress and Biancamaria Ricci and Kai Sun and Tong Yang and Chun Wang and Jianqiu Xiao and Yousef Abu-Amer and Gabriel Mbalaviele",
note = "Funding Information: This work was supported by NIH/NIAMS AR068972 and AR076758 grants to GM. YA‐A was supported by NIH grants AR049192, AR072623, and #85160 grant from the Shriners Hospital for Children. The histology & morphometry and structure & strength cores at Washington University Musculoskeletal Research Center are supported by P30 AR074992 grant. We thank Dr V. M. Dixit (Genentech, South San Francisco, CA) and Dr Dr Russel Vance (University of California, Berkeley, CA). Funding Information: This work was supported by NIH/NIAMS AR068972 and AR076758 grants to GM. YA-A was supported by NIH grants AR049192, AR072623, and #85160 grant from the Shriners Hospital for Children. The histology & morphometry and structure & strength cores at Washington University Musculoskeletal Research Center are supported by P30 AR074992 grant. We thank Dr V. M. Dixit (Genentech, South San Francisco, CA) and Dr Dr Russel Vance (University of California, Berkeley, CA). Publisher Copyright: {\textcopyright} 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology",
year = "2021",
month = sep,
doi = "10.1096/fj.202100767RR",
language = "English",
volume = "35",
journal = "FASEB Journal",
issn = "0892-6638",
number = "9",
}