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© Research
Publication : eLife

A trans-eQTL network regulates osteoclast multinucleation and bone mass.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in eLife - 19 Jun 2020

Pereira M, Ko JH, Logan J, Protheroe H, Kim KB, Tan ALM, Croucher PI, Park KS, Rotival M, Petretto E, Bassett JD, Williams GR, Behmoaras J,

Link to Pubmed [PMID] – 32553114

Link to DOI [DOI] – 10.7554/eLife.55549e55549

Elife 2020 06; 9():

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 trans-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 Bcat1 and seven other co-regulated MMnet genes out of 13, regulate bone function. Specifically, global (Pik3cb-/-, Atp8b2+/-, Igsf8-/-, Eml1-/-, Appl2-/-, Deptor-/-) and myeloid-specific Slc40a1 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.

https://pubmed.ncbi.nlm.nih.gov/32553114