{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T23:00:03Z","timestamp":1776466803563,"version":"3.51.2"},"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2014,1,28]],"date-time":"2014-01-28T00:00:00Z","timestamp":1390867200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0087311","type":"journal-article","created":{"date-parts":[[2014,1,28]],"date-time":"2014-01-28T21:42:57Z","timestamp":1390945377000},"page":"e87311","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":28,"title":["A Ser252Trp Mutation in Fibroblast Growth Factor Receptor 2 (FGFR2) Mimicking Human Apert Syndrome Reveals an Essential Role for FGF Signaling in the Regulation of Endochondral Bone Formation"],"prefix":"10.1371","volume":"9","author":[{"given":"Peng","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tujun","family":"Weng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shichang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shijin","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingtao","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lianyang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2014,1,28]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1093\/hmg\/8.1.35","article-title":"A Lys644Glu substitution in fibroblast growth factor receptor 3 (FGFR3) causes dwarfism in mice by activation of STATs and ink4 cell cycle inhibitors","volume":"8","author":"C Li","year":"1999","journal-title":"Hum Mol Genet"},{"key":"ref2","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":"M Muenke","year":"1995","journal-title":"Trends Genet"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1093\/hmg\/ddp590","article-title":"Gain-of-function mutation in FGFR3 in mice leads to decreased bone mass by affecting both osteoblastogenesis and osteoclastogenesis","volume":"19","author":"N Su","year":"2010","journal-title":"Hum Mol Genet"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1002\/ajmg.1320470509","article-title":"Skeletal abnormalities in the Apert syndrome","volume":"47","author":"MM Cohen Jr","year":"1993","journal-title":"Am J Med Genet"},{"key":"ref5","doi-asserted-by":"crossref","unstructured":"Cohen MM Jr (1988) Craniosynostosis update 1987. Am J Med Genet Suppl 4: 99\u2013148.","DOI":"10.1002\/ajmg.1320310514"},{"key":"ref6","first-page":"321","article-title":"Analysis of phenotypic features and FGFR2 mutations in Apert syndrome","volume":"57","author":"WJ Park","year":"1995","journal-title":"Am J Hum Genet"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"3641","DOI":"10.1073\/pnas.081082498","article-title":"Uncoupling fibroblast growth factor receptor 2 ligand binding specificity leads to Apert syndrome-like phenotypes","volume":"98","author":"K Yu","year":"2001","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"3783","DOI":"10.1242\/dev.129.16.3783","article-title":"The IIIc alternative of Fgfr2 is a positive regulator of bone formation","volume":"129","author":"VP Eswarakumar","year":"2002","journal-title":"Development"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"3537","DOI":"10.1242\/dev.01914","article-title":"Abnormalities in cartilage and bone development in the Apert syndrome FGFR2(+\/S252W) mouse","volume":"132","author":"Y Wang","year":"2005","journal-title":"Development"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/j.bone.2010.11.014","article-title":"The primary site of the acrocephalic feature in Apert Syndrome is a dwarf cranial base with accelerated chondrocytic differentiation due to aberrant activation of the FGFR2 signaling","volume":"48","author":"M Nagata","year":"2011","journal-title":"Bone"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.bone.2007.11.019","article-title":"A Pro253Arg mutation in fibroblast growth factor receptor 2 (Fgfr2) causes skeleton malformation mimicking human Apert syndrome by affecting both chondrogenesis and osteogenesis","volume":"42","author":"L Yin","year":"2008","journal-title":"Bone"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.bone.2006.10.013","article-title":"Fibroblast growth factor expression in the postnatal growth plate","volume":"40","author":"JE Lazarus","year":"2007","journal-title":"Bone"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/S8756-3282(03)00163-7","article-title":"Fgfr mRNA isoforms in craniofacial bone development","volume":"33","author":"DP Rice","year":"2003","journal-title":"Bone"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"4897","DOI":"10.1074\/jbc.M805432200","article-title":"Fibroblast growth factor receptor 2 promotes osteogenic differentiation in mesenchymal cells via ERK1\/2 and protein kinase C signaling","volume":"284","author":"H Miraoui","year":"2009","journal-title":"J Biol Chem"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"REVIEWS3005","DOI":"10.1186\/gb-2001-2-3-reviews3005","article-title":"Fibroblast growth factors","volume":"2","author":"DM Ornitz","year":"2001","journal-title":"Genome Biol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/1471-213X-10-22","article-title":"Activation of p38 MAPK pathway in the skull abnormalities of Apert syndrome Fgfr2(+P253R) mice","volume":"10","author":"Y Wang","year":"2010","journal-title":"BMC Dev Biol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1006\/excr.2000.4820","article-title":"The Ser252Trp fibroblast growth factor receptor-2 (FGFR-2) mutation induces PKC-independent downregulation of FGFR-2 associated with premature calvaria osteoblast differentiation","volume":"256","author":"J Lemonnier","year":"2000","journal-title":"Exp Cell Res"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1101\/gad.990702","article-title":"FGF signaling pathways in endochondral and intramembranous bone development and human genetic disease","volume":"16","author":"DM Ornitz","year":"2002","journal-title":"Genes Dev"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S8756-3282(03)00222-9","article-title":"A Ser252Trp [corrected] substitution in mouse fibroblast growth factor receptor 2 (Fgfr2) results in craniosynostosis","volume":"33","author":"L Chen","year":"2003","journal-title":"Bone"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1172\/JCI8641","article-title":"Disruption of the fibroblast growth factor-2 gene results in decreased bone mass and bone formation","volume":"105","author":"A Montero","year":"2000","journal-title":"J Clin Invest"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.bbrc.2006.01.044","article-title":"Impaired bone anabolic response to parathyroid hormone in Fgf2-\/- and Fgf2+\/\u2212 mice","volume":"341","author":"MM Hurley","year":"2006","journal-title":"Biochem Biophys Res Commun"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.bbrc.2008.08.165","article-title":"Gain-of-function mutation of FGFR3 results in impaired fracture healing due to inhibition of chondrocyte differentiation","volume":"376","author":"N Su","year":"2008","journal-title":"Biochem Biophys Res Commun"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1359\/jbmr.1997.12.1.96","article-title":"Localization and quantification of proliferating cells during rat fracture repair: detection of proliferating cell nuclear antigen by immunohistochemistry","volume":"12","author":"A Iwaki","year":"1997","journal-title":"J Bone Miner Res"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/371252a0","article-title":"Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia","volume":"371","author":"F Rousseau","year":"1994","journal-title":"Nature"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"5443","DOI":"10.1093\/hmg\/dds390","article-title":"A novel FGFR3-binding peptide inhibits FGFR3 signaling and reverses the lethal phenotype of mice mimicking human thanatophoric dysplasia","volume":"21","author":"M Jin","year":"2012","journal-title":"Hum Mol Genet"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1093\/hmg\/10.5.457","article-title":"A Ser(365)\u2013>Cys mutation of fibroblast growth factor receptor 3 in mouse downregulates Ihh\/PTHrP signals and causes severe achondroplasia","volume":"10","author":"L Chen","year":"2001","journal-title":"Hum Mol Genet"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"5860","DOI":"10.1073\/pnas.93.12.5860","article-title":"Efficient in vivo manipulation of mouse genomic sequences at the zygote stage","volume":"93","author":"M Lakso","year":"1996","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"3063","DOI":"10.1242\/dev.00491","article-title":"Conditional inactivation of FGF receptor 2 reveals an essential role for FGF signaling in the regulation of osteoblast function and bone growth","volume":"130","author":"K Yu","year":"2003","journal-title":"Development"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1634\/stemcells.19-3-180","article-title":"Bone marrow stromal stem cells: nature, biology, and potential applications","volume":"19","author":"P Bianco","year":"2001","journal-title":"Stem Cells"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"539","DOI":"10.2217\/17460751.1.4.539","article-title":"Osteogenic differentiation of human marrow-derived mesenchymal stem cells","volume":"1","author":"PJ Marie","year":"2006","journal-title":"Regen Med"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"2896","DOI":"10.1634\/stemcells.2007-0637","article-title":"Concise review: mesenchymal stem\/multipotent stromal cells: the state of transdifferentiation and modes of tissue repair\u2013current views","volume":"25","author":"DG Phinney","year":"2007","journal-title":"Stem Cells"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"8695","DOI":"10.1074\/jbc.275.12.8695","article-title":"Cbfa1 is a positive regulatory factor in chondrocyte maturation","volume":"275","author":"H Enomoto","year":"2000","journal-title":"J Biol Chem"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"36181","DOI":"10.1074\/jbc.M206057200","article-title":"Fibroblast growth factor 2 induction of the osteocalcin gene requires MAPK activity and phosphorylation of the osteoblast transcription factor, Cbfa1\/Runx2","volume":"277","author":"G Xiao","year":"2002","journal-title":"J Biol Chem"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"12555","DOI":"10.1073\/pnas.0405031101","article-title":"A gain-of-function mutation of Fgfr2c demonstrates the roles of this receptor variant in osteogenesis","volume":"101","author":"VP Eswarakumar","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1146\/annurev.cellbio.16.1.191","article-title":"Bone development","volume":"16","author":"BR Olsen","year":"2000","journal-title":"Annu Rev Cell Dev Biol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1083\/jcb.149.6.1297","article-title":"Signaling by fibroblast growth factors (FGF) and fibroblast growth factor receptor 2 (FGFR2)-activating mutations blocks mineralization and induces apoptosis in osteoblasts","volume":"149","author":"A Mansukhani","year":"2000","journal-title":"J Cell Biol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"4456","DOI":"10.1210\/endo.138.10.5425","article-title":"Fibroblast growth factor-2 supports ex vivo expansion and maintenance of osteogenic precursors from human bone marrow","volume":"138","author":"I Martin","year":"1997","journal-title":"Endocrinology"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1083\/jcb.200409182","article-title":"Sox2 induction by FGF and FGFR2 activating mutations inhibits Wnt signaling and osteoblast differentiation","volume":"168","author":"A Mansukhani","year":"2005","journal-title":"J Cell Biol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.ydbio.2006.05.031","article-title":"Fibroblast growth factor receptor 1 signaling in the osteo-chondrogenic cell lineage regulates sequential steps of osteoblast maturation","volume":"296","author":"AL Jacob","year":"2006","journal-title":"Dev Biol"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1016\/S0002-9440(10)64139-9","article-title":"Increased osteoblast apoptosis in apert craniosynostosis: role of protein kinase C and interleukin-1","volume":"158","author":"J Lemonnier","year":"2001","journal-title":"Am J Pathol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1359\/jbmr.2001.16.5.832","article-title":"Role of N-cadherin and protein kinase C in osteoblast gene activation induced by the S252W fibroblast growth factor receptor 2 mutation in Apert craniosynostosis","volume":"16","author":"J Lemonnier","year":"2001","journal-title":"J Bone Miner Res"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1038\/ng2096","article-title":"RNA interference and inhibition of MEK-ERK signaling prevent abnormal skeletal phenotypes in a mouse model of craniosynostosis","volume":"39","author":"V Shukla","year":"2007","journal-title":"Nat Genet"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"2842","DOI":"10.2741\/2890","article-title":"FGF signaling: its role in bone development and human skeleton diseases","volume":"13","author":"N Su","year":"2008","journal-title":"Front Biosci"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1074\/jbc.M310384200","article-title":"Activation of the ERK1\/2 and p38 mitogen-activated protein kinase pathways mediates fibroblast growth factor-induced growth arrest of chondrocytes","volume":"279","author":"A Raucci","year":"2004","journal-title":"J Biol Chem"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1210\/en.2006-1000","article-title":"p38 mitogen-activated protein kinase regulates osteoblast differentiation through osterix","volume":"148","author":"X Wang","year":"2007","journal-title":"Endocrinology"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"5613","DOI":"10.1074\/jbc.275.8.5613","article-title":"Opposing role of mitogen-activated protein kinase subtypes, erk-1\/2 and p38, in the regulation of chondrogenesis of mesenchymes","volume":"275","author":"CD Oh","year":"2000","journal-title":"J Biol Chem"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0087311","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,24]],"date-time":"2022-03-24T16:25:55Z","timestamp":1648139155000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0087311"}},"subtitle":[],"editor":[{"given":"Laszlo","family":"Buday","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2014,1,28]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2014,1,28]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0087311","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,1,28]]}}}