PubMed 25131209

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: SK4

Title: Kcnn4 is a regulator of macrophage multinucleation in bone homeostasis and inflammatory disease.

Authors: Heeseog Kang, Audrey Kerloc'h, Maxime Rotival, Xiaoqing Xu, Qing Zhang, Zelpha D'Souza, Michael Kim, Jodi Carlson Scholz, Jeong-Hun Ko, Prashant K Srivastava, Jonathan R Genzen, Weiguo Cui, Timothy J Aitman, Laurence Game, James E Melvin, Adedayo Hanidu, Janice Dimock, Jie Zheng, Donald Souza, Aruna K Behera, Gerald Nabozny, H Terence Cook, J H Duncan Bassett, Graham R Williams, Jun Li, Agnès Vignery, Enrico Petretto, Jacques Behmoaras

Journal, date & volume: Cell Rep, 2014 Aug 21 , 8, 1210-24

PubMed link:

Macrophages can fuse to form osteoclasts in bone or multinucleate giant cells (MGCs) as part of the immune response. We use a systems genetics approach in rat macrophages to unravel their genetic determinants of multinucleation and investigate their role in both bone homeostasis and inflammatory disease. We identify a trans-regulated gene network associated with macrophage multinucleation and Kcnn4 as being the most significantly trans-regulated gene in the network and induced at the onset of fusion. Kcnn4 is required for osteoclast and MGC formation in rodents and humans. Genetic deletion of Kcnn4 reduces macrophage multinucleation through modulation of Ca(2+) signaling, increases bone mass, and improves clinical outcome in arthritis. Pharmacological blockade of Kcnn4 reduces experimental glomerulonephritis. Our data implicate Kcnn4 in macrophage multinucleation, identifying it as a potential therapeutic target for inhibition of bone resorption and chronic inflammation.