| First Author | Pereira M | Year | 2020 |
| Journal | Elife | Volume | 9 |
| PubMed ID | 32553114 | Mgi Jnum | J:292114 |
| Mgi Id | MGI:6442402 | Doi | 10.7554/eLife.55549 |
| Citation | Pereira M, et al. (2020) A trans-eQTL network regulates osteoclast multinucleation and bone mass. Elife 9:e55549 |
| abstractText | 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. |
