| First Author | Nakamura S | Year | 2017 |
| Journal | PLoS One | Volume | 12 |
| Issue | 4 | Pages | e0175632 |
| PubMed ID | 28414795 | Mgi Jnum | J:245652 |
| Mgi Id | MGI:5916191 | Doi | 10.1371/journal.pone.0175632 |
| Citation | Nakamura S, et al. (2017) Negative feedback loop of bone resorption by NFATc1-dependent induction of Cadm1. PLoS One 12(4):e0175632 |
| abstractText | Trimethylation of histone H3 lysine 4 and lysine 27 (H3K4me3 and H3K27me3) at gene promoter regions critically regulates gene expression. Key developmental genes tend to exhibit changes in histone modification patterns from the H3K4me3/H3K27me3 bivalent pattern to the H3K4me3 monovalent pattern. Using comprehensive chromatin immunoprecipitation followed by sequencing in bone marrow-derived macrophages (BMMs) and mature osteoclasts, we found that cell surface adhesion molecule 1 (Cadm1) is a direct target of nuclear factor of activated T cells 1 (NFATc1) and exhibits a bivalent histone pattern in BMMs and a monovalent pattern in osteoclasts. Cadm1 expression was upregulated in BMMs by receptor activator of nuclear factor kappa B ligand (RANKL), and blocked by a calcineurin/NFATc1 inhibitor, FK506. Cadm1-deficient mice exhibited significantly reduced bone mass compared with wild-type mice, which was due to the increased osteoclast differentiation, survival and bone-resorbing activity in Cadm1-deficient osteoclasts. These results suggest that Cadm1 is a direct target of NFATc1, which is induced by RANKL through epigenetic modification, and regulates osteoclastic bone resorption in a negative feedback manner. |
