A Trans-eQTL Network Regulates Osteoclast Multinucleation and Bone Mass

Overview

Journal Elife

Specialty Biology

Date 2020 Jun 20

PMID 32553114

Citations 19

Authors

Marie Pereira

Jeong-Hun Ko

John Logan

Hayley Protheroe

Kee-Beom Kim

Amelia Li Min Tan

Peter I Croucher

Kwon-Sik Park

Maxime Rotival

Enrico Petretto

Jh Duncan Bassett

Graham R Williams

Jacques Behmoaras

Affiliations

Soon will be listed here.

Abstract

Functional characterisation of cell-type-specific regulatory networks is key to establish a causal link between genetic variation and phenotype. The osteoclast offers a unique model for interrogating the contribution of co-regulated genes to in vivo phenotype as its multinucleation and resorption activities determine quantifiable skeletal traits. Here we took advantage of a -regulated gene network (MMnet, macrophage multinucleation network) which we found to be significantly enriched for GWAS variants associated with bone-related phenotypes. We found that the network hub gene and seven other co-regulated MMnet genes out of 13, regulate bone function. Specifically, global (, , , , , ) and myeloid-specific knockout mice displayed abnormal bone phenotypes. We report opposing effects of MMnet genes on bone mass in mice and osteoclast multinucleation/resorption in humans with strong correlation between the two. These results identify MMnet as a functionally conserved network that regulates osteoclast multinucleation and bone mass.

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