{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T17:03:18Z","timestamp":1781974998970,"version":"3.54.5"},"reference-count":54,"publisher":"The Endocrine Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Transgenic mice harboring high molecular weight fibroblast growth factor (FGF)2 isoforms (HMWTg) in osteoblast lineage cells phenocopy human X-linked hypophosphatemic rickets (XLH) and Hyp murine model of XLH demonstrating increased FGF23\/FGF receptor signaling and hypophosphatemic rickets. Because HMWFGF2 was upregulated in bones of Hyp mice and abnormal FGF receptor (FGFR) signaling is important in XLH, HMWTg mice were used to examine the effect of the FGFR inhibitor NVP-BGJ398, now in clinical trials for cancer therapy, on hypophosphatemic rickets. Short-term treatment with NVP-BGJ398 rescued abnormal FGFR signaling and hypophosphatemia in HMWTg. Long-term treatment with NVP-BGJ398 normalized tail, tibia, and femur length. Four weeks NVP-BGJ398 treatment significantly increased total body bone mineral density (BMD) and bone mineral content (BMC) in HMWTg mice; however, at 8 weeks, total body BMD and BMC was indistinguishable among groups. Micro-computed tomography revealed decreased vertebral bone volume, trabecular number, and increased trabecular spacing, whereas femur trabecular tissue density was increased; however, NVP-BGJ398 rescued defective cortical bone mineralization, increased thickness, reduced porosity, and increased endosteal perimeter and cortical tissue density in HMWTg. NVP-BGJ398 improved femur cancellous bone, cortical bone structure, growth plate, and double labeling in cortical bone and also increased femur trabeculae double labeled surface, mineral apposition rate, bone formation rate, and osteoclast number and surface in HMWTg. The decreased NPT2a protein that is important for renal phosphate excretion was rescued by NVP-BGJ398 treatment. We conclude that NVP-BGJ398 partially rescued hypophosphatemic rickets in HMWTg. However, long-term treatment with NVP-BGJ398 further increased serum FGF23 that could exacerbate the mineralization defect.<\/jats:p>","DOI":"10.1210\/en.2016-1617","type":"journal-article","created":{"date-parts":[[2017,8,14]],"date-time":"2017-08-14T18:09:25Z","timestamp":1502734165000},"page":"3629-3646","source":"Crossref","is-referenced-by-count":8,"title":["Inhibition of FGFR Signaling Partially Rescues Hypophosphatemic Rickets in HMWFGF2 Tg Male Mice"],"prefix":"10.1210","volume":"158","author":[{"given":"Liping","family":"Xiao","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Connecticut School of Medicine, UConn Health, Farmington, Connecticut, 06030-052"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erxia","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Connecticut School of Medicine, UConn Health, Farmington, Connecticut, 06030-052"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Collin","family":"Homer-Bouthiette","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Connecticut School of Medicine, UConn Health, Farmington, Connecticut, 06030-052"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marja M","family":"Hurley","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Connecticut School of Medicine, UConn Health, Farmington, Connecticut, 06030-052"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2017,8,14]]},"reference":[{"key":"2020071620292852100_B1","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1146\/annurev.med.051308.111339","article-title":"Regulation of phosphate homeostasis by PTH, vitamin D, and FGF23","volume":"61","author":"Bergwitz","year":"2010","journal-title":"Ann Rev Med"},{"key":"2020071620292852100_B2","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/B978-012098652-1.50149-9","volume-title":"Principles of Bone Biology","author":"Hurley","year":"2002"},{"issue":"8","key":"2020071620292852100_B3","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/S0168-9525(00)89088-5","article-title":"Fibroblast-growth-factor receptor mutations in human skeletal disorders","volume":"11","author":"Muenke","year":"1995","journal-title":"Trends Genet"},{"issue":"3","key":"2020071620292852100_B4","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/S0959-437X(97)80152-9","article-title":"Skeletal disorders associated with fibroblast growth factor receptor mutations","volume":"7","author":"De Moerlooze","year":"1997","journal-title":"Curr Opin Genet Dev"},{"issue":"12","key":"2020071620292852100_B5","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1091\/mbc.6.12.1861","article-title":"Abnormal bone growth and selective translational regulation in basic fibroblast growth factor (FGF-2) transgenic mice","volume":"6","author":"Coffin","year":"1995","journal-title":"Mol Biol Cell"},{"issue":"2","key":"2020071620292852100_B6","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.cytogfr.2005.01.002","article-title":"FGF23 and disorders of phosphate homeostasis","volume":"16","author":"Yu","year":"2005","journal-title":"Cytokine Growth Factor Rev"},{"issue":"3","key":"2020071620292852100_B7","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/81664","article-title":"Autosomal dominant hypophosphatemic rickets is associated with mutations in FGF23","volume":"26","author":"ADHR Consortium","year":"2000","journal-title":"Nat Genet"},{"issue":"11","key":"2020071620292852100_B8","doi-asserted-by":"crossref","first-page":"6500","DOI":"10.1073\/pnas.101545198","article-title":"Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia","volume":"98","author":"Shimada","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071620292852100_B9","doi-asserted-by":"crossref","unstructured":"A gene (PEX) with homologies to endopeptidases is mutated in patients with X-linked hypophosphatemic rickets. 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