Kruppel-like factor 3 inhibition by mutated lncRNA <i>Reg1cp</i> results in human high bone mass syndrome.

ABSTRACT: High bone mass (HBM) is usually caused by gene mutations, and its mechanism remains unclear. In the present study, we identified a novel mutation in the long noncoding RNA Reg1cp that is associated with HBM. Subsequent analysis in 1,465 Chinese subjects revealed that heterozygous Reg1cp individuals had higher bone density compared with subjects with WT Reg1cp Mutant Reg1cp increased the formation of the CD31^hiEmcn^hi endothelium in the bone marrow, which stimulated angiogenesis during osteogenesis. Mechanistically, mutant Reg1cp directly binds to Krüppel-like factor 3 (KLF3) to inhibit its activity. Mice depleted of Klf3 in endothelial cells showed a high abundance of CD31^hiEmcn^hi vessels and increased bon

SUBMITTER: Yang M 

PROVIDER: S-EPMC6683986 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature