{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T02:10:19Z","timestamp":1768875019377,"version":"3.49.0"},"reference-count":68,"publisher":"The Endocrine Society","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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\u2212\/\u2212 mice exhibit expanded bone marrow populations of osteoprogenitors and supporting CD8+ T cells. To determine whether the Nmp4\u2212\/\u2212 phenotype persists in an osteoporosis model we compared PTH response in ovariectomized (ovx) wild-type (WT) and Nmp4\u2212\/\u2212 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\u2212\/\u2212 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\u2212\/\u2212 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\u2212\/\u2212 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\u2212\/\u2212 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.<\/jats:p>","DOI":"10.1210\/me.2014-1406","type":"journal-article","created":{"date-parts":[[2015,8,5]],"date-time":"2015-08-05T17:00:58Z","timestamp":1438794058000},"page":"1269-1285","source":"Crossref","is-referenced-by-count":14,"title":["Genome-Wide Mapping and Interrogation of the Nmp4 Antianabolic Bone Axis"],"prefix":"10.1210","volume":"29","author":[{"given":"Paul","family":"Childress","sequence":"first","affiliation":[{"name":"Department 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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith R.","family":"Stayrook","sequence":"first","affiliation":[{"name":"Lilly Research Laboratories (K.R.S., J.K.M., Z.R.G., V.K.), Eli Lilly and Company, Indianapolis, Indiana 46202"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta B.","family":"Alvarez","sequence":"first","affiliation":[{"name":"Orthopaedic Surgery (M.B.A.), Indiana University School of Medicine Indiana 46202"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiping","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Medical and Molecular Genetics (Z.W., Y.S., Y.L., J.P.B.), Indiana University School of Medicine Indiana 46202"},{"name":"Center for Computational Biology and Bioinformatics (Z.W., Y.L.), Indiana University School of Medicine Indiana 46202"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Shao","sequence":"first","affiliation":[{"name":"Department of Medical and Molecular Genetics (Z.W., Y.S., Y.L., J.P.B.), Indiana University School of Medicine Indiana 46202"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Selene","family":"Hernandez-Buquer","sequence":"first","affiliation":[{"name":"Department 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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin K.","family":"Mack","sequence":"first","affiliation":[{"name":"Lilly Research Laboratories (K.R.S., J.K.M., Z.R.G., V.K.), Eli Lilly and Company, Indianapolis, Indiana 46202"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zachary R.","family":"Grese","sequence":"first","affiliation":[{"name":"Lilly Research Laboratories (K.R.S., J.K.M., Z.R.G., V.K.), Eli Lilly and Company, Indianapolis, Indiana 46202"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongzheng","family":"He","sequence":"first","affiliation":[{"name":"; Department of Pediatrics (Y.H., F.-C.Y.), Indiana University School of Medicine Indiana 46202"},{"name":"Herman B Wells Center for Pediatric Research (Y.H., F.-C.Y.); Indiana University Indianapolis, Indiana 46202"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Horan","sequence":"first","affiliation":[{"name":"Department 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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fredrick M.","family":"Pavalko","sequence":"first","affiliation":[{"name":"Cellular and Integrative Physiology (F.M.P.); Indiana University Indianapolis, Indiana 46202"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stuart J.","family":"Warden","sequence":"first","affiliation":[{"name":"Center for Translational Musculoskeletal Research (S.J.W.), School of Health and Rehabilitation Sciences, Indiana University Indianapolis, Indiana 46202"},{"name":"Department of Physical Therapy (S.J.W.), School of Health and Rehabilitation Sciences, Indiana University, Indianapolis, Indiana 46202"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander G.","family":"Robling","sequence":"first","affiliation":[{"name":"Department 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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng-Chun","family":"Yang","sequence":"first","affiliation":[{"name":"; Department of Pediatrics (Y.H., F.-C.Y.), Indiana University School of Medicine Indiana 46202"},{"name":"Herman B Wells Center for Pediatric Research (Y.H., F.-C.Y.); Indiana University Indianapolis, Indiana 46202"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew R.","family":"Allen","sequence":"first","affiliation":[{"name":"Department 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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Venkatesh","family":"Krishnan","sequence":"first","affiliation":[{"name":"Lilly Research Laboratories (K.R.S., J.K.M., Z.R.G., V.K.), Eli Lilly and Company, Indianapolis, Indiana 46202"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunlong","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Medical and Molecular Genetics (Z.W., Y.S., Y.L., J.P.B.), Indiana University School of Medicine Indiana 46202"},{"name":"Center for Computational Biology and Bioinformatics (Z.W., Y.L.), Indiana University School of Medicine Indiana 46202"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph P.","family":"Bidwell","sequence":"first","affiliation":[{"name":"Department 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"},{"name":"Department of Medical 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