Cross?talk Between Histone and <scp>DNA</scp> Methylation Mediates Bone Loss in Hind Limb Unloading

Bone loss induced by mechanical unloading is a common skeletal disease, but the precise mechanism remains unclear. The current study investigated role of histone methylation, key epigenetic marker, and its cross-talk with DNA methylation in bone unloading. expression G9a, ubiquitin-like PHD ring finger domains 1 (UHRF1), transferase (DNMT1) were increased hind limb (HLU) rats. This was accompanied an level H3 lysine 9 (H3K9) di-/tri-methylation at lncH19 promoter. Then, alteration DNMT1, or UHRF1 significantly affected osteogenic activity UMR106 cells. Osteogenic gene matrix mineralization robustly promoted after simultaneous knockdown UHRF1. Furthermore, physical interactions promoter G9a as well direct among detected. Importantly, overexpression UHRF1, respectively, resulted enrichment H3K9me2/me3 5-methylcytosine Finally, vivo rescue experiments indicated that relieved HLU In conclusion, our research demonstrated critical H3K9 regulating Combined targeting could be promising strategy for treatment © 2021 American Society Mineral Research (ASBMR).