Fig. 3.

The Ingenuity Pathway Analysis Molecule Activity Predictor algorithm indicated that loss of nuclear matrix protein 4 (Nmp4) elevates Wnt/β-catenin activity, a major driver of bone anabolism and suppressor of adipogenesis. Molecules in pink-red are found in the data set and are upregulated. Molecules that are green are found in the data set and are downregulated. Molecules that are gray are found in the data set but did not pass any of the filter parameters originally established for the analysis. White molecules are not in the data set but part of the pathway. Orange molecules and arrows predict activation whereas blue molecules and arrows predict inhibition. On the right side of this pathway is a heatmap of genes comprising the Wnt/β-catenin pathway derived from the RNA-seq data of wild-type (WT) and Nmp4^−/− MPSCs at day 3 (uncommitted) and day 7 (early osteogenesis) in culture. Red boxes indicate increased expression in the Nmp4^−/− cells compared with the WT, with greater color saturation indicating higher expression, and green color indicates reduced expression. The star indicates Nmp4 binds proximal to the transcription start site or within the intron of the gene as determined by chromatin immunoprecipitation sequencing (ChIP-seq) analysis [Childress et al. (16)]. APC, adenomatous polyposis coli protein; BCL9, B-cell lymphoma 9; CBP, histone acetyl transferase; CKI, casein kinase I; Dkk, Dickkopf; Dsh, disheveled; GSK3β, glycogen synthase kinase 3β; GBP, GSK3 binding protein; Hpk1 a.k.a. Map4k1, mitogen-activated protein kinase kinase kinase kinase 1; NLK, NEMO-like kinase; RAR, retinoic acid receptor; Tak1 a.k.a. Nr2c2, nuclear receptor subfamily 2, group C, member 2; TCF, T-cell activation factor; TGF-β, transforming growth factor-β.