GSE133212 Conditional Activation of NF-kB Inducing Kinase (NIK) in the Osteolineage Enhances both Basal and Loading-Induced Bone Formation

Contributors : Jennifer L Davis ; Linda Cox ; Christine Shao ; Cheng Lyu ; Shaopeng Liu ; Rajeev Aurora ; Deborah J VeisSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusStudies from global loss-of-function mutants suggest that alternative NF-kB downstream of NF-kB inducing kinase (NIK) is a cell-intrinsic negative regulator of osteogenesis. However, the interpretation of the osteoblast and/or osteocyte contribution to the bone phenotype is complicated by simultaneous osteoclast defects in these models. Therefore, we turned to a transgenic mouse model to investigate the direct role of NIK in the osteolineage. Osx-Cre;NT3 animals (NT3-Cre+), which bear a constitutively active NIK allele (NT3) driven by Osx-Cre, were compared to their Cre-negative, Control (Ctrl) littermates. NT3-Cre+ mice had elevated serum P1NP and CTX levels. Despite this high turnover state, microCT showed that constitutive activation of NIK resulted in a net increase in basal bone mass in both cortical and cancellous compartments. Furthermore, NT3-Cre+ mice exhibited a greater anabolic response following mechanical loading compared to controls. We next performed RNA-Seq on non-loaded and loaded tibiae to elucidate possible mechanisms underlying the increased bone anabolism seen in NT3-Cre+ mice. Hierarchical clustering revealed two main transcriptional programs: one loading-responsive and the other NT3 transgene-driven. Gene ontology (GO) analysis indica...

Source: GEO: Gene Expression Omnibus - June 25, 2019 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research