Related Experiment Video
Updated: Apr 5, 2026
![Quantitative [18F]-Naf-PET-MRI Analysis for the Evaluation of Dynamic Bone Turnover in a Patient with Facetogenic Low Back Pain](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F58491.jpg&w=3840&q=50)
Quantitative [18F]-Naf-PET-MRI Analysis for the Evaluation of Dynamic Bone Turnover in a Patient with Facetogenic Low Back Pain
Published on: August 8, 2019
Genome-Wide Mapping and Interrogation of the Nmp4 Antianabolic Bone Axis
Paul Childress1, Keith R Stayrook1, Marta B Alvarez1
1Department of Anatomy and Cell Biology (P.C., S.H.-B., D.H., A.G.R., M.R.A., J.P.B.), Indiana University School of Medicine, Indianapolis, Indiana 46202; Lilly Research Laboratories (K.R.S., J.K.M., Z.R.G., V.K.), Eli Lilly and Company, Indianapolis, Indiana 46202; Orthopaedic Surgery (M.B.A.), Indiana University School of Medicine; Department of Medical and Molecular Genetics (Z.W., Y.S., Y.L., J.P.B.), Indiana University School of Medicine; Center for Computational Biology and Bioinformatics (Z.W., Y.L.), Indiana University School of Medicine; Department of Pediatrics (Y.H., F.-C.Y.), Indiana University School of Medicine; Herman B Wells Center for Pediatric Research (Y.H., F.-C.Y.); Cellular and Integrative Physiology (F.M.P.); Center for Translational Musculoskeletal Research (S.J.W.), School of Health and Rehabilitation Sciences, Indiana University; and Department of Physical Therapy (S.J.W.), School of Health and Rehabilitation Sciences, Indiana University, Indianapolis, Indiana 46202.
Abstract:
PTH is an osteoanabolic for treating osteoporosis but its potency wanes. Disabling the transcription factor nuclear matrix protein 4 (Nmp4) in healthy, ovary-intact mice enhances bone response to PTH and bone morphogenetic protein 2 and protects from unloading-induced osteopenia. These Nmp4(-/-) mice exhibit expanded bone marrow populations of osteoprogenitors and supporting CD8(+) T cells. To determine whether the Nmp4(-/-) phenotype persists in an osteoporosis model we compared PTH response in ovariectomized (ovx) wild-type (WT) and Nmp4(-/-) mice. To identify potential Nmp4 target genes, we performed bioinformatic/pathway profiling on Nmp4 chromatin immunoprecipitation sequencing (ChIP-seq) data. Mice (12 w) were ovx or sham operated 4 weeks before the initiation of PTH therapy. Skeletal phenotype analysis included microcomputed tomography, histomorphometry, serum profiles, fluorescence-activated cell sorting and the growth/mineralization of cultured WT and Nmp4(-/-) bone marrow mesenchymal stem progenitor cells (MSPCs). ChIP-seq data were derived using MC3T3-E1 preosteoblasts, murine embryonic stem cells, and 2 blood cell lines. Ovx Nmp4(-/-) mice exhibited an improved response to PTH coupled with elevated numbers of osteoprogenitors and CD8(+) T cells, but were not protected from ovx-induced bone loss. Cultured Nmp4(-/-) MSPCs displayed enhanced proliferation and accelerated mineralization. ChIP-seq/gene ontology analyses identified target genes likely under Nmp4 control as enriched for negative regulators of biosynthetic processes. Interrogation of mRNA transcripts in nondifferentiating and osteogenic differentiating WT and Nmp4(-/-) MSPCs was performed on 90 Nmp4 target genes and differentiation markers. These data suggest that Nmp4 suppresses bone anabolism, in part, by regulating IGF-binding protein expression. Changes in Nmp4 status may lead to improvements in osteoprogenitor response to therapeutic cues.
