{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T01:26:00Z","timestamp":1780622760154,"version":"3.54.1"},"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2015,2,18]],"date-time":"2015-02-18T00:00:00Z","timestamp":1424217600000},"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.0117016","type":"journal-article","created":{"date-parts":[[2015,2,18]],"date-time":"2015-02-18T19:18:24Z","timestamp":1424287104000},"page":"e0117016","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":36,"title":["Increased Classical Endoplasmic Reticulum Stress Is Sufficient to Reduce Chondrocyte Proliferation Rate in the Growth Plate and Decrease Bone Growth"],"prefix":"10.1371","volume":"10","author":[{"given":"Louise H. W.","family":"Kung","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Helen","family":"Rajpar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Preziosi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Briggs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond P.","family":"Boot-Handford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2015,2,18]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1146\/annurev.cellbio.21.122303.120200","article-title":"Intracellular signaling by the unfolded protein response","volume":"22","author":"S Bernales","year":"2006","journal-title":"Annu Rev Cell Dev Biol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1016\/j.semcdb.2007.09.003","article-title":"The endoplasmic reticulum and the unfolded protein response","volume":"18","author":"JD Malhotra","year":"2007","journal-title":"Semin Cell Dev Biol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/nrm2199","article-title":"Signal integration in the endoplasmic reticulum unfolded protein response","volume":"8","author":"D Ron","year":"2007","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1007\/s00018-007-7383-5","article-title":"Endoplasmic reticulum stress responses","volume":"65","author":"M Schroeder","year":"2008","journal-title":"Cell Mol Life Sci"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s00441-009-0877-8","article-title":"The unfolded protein response and its relevance to connective tissue diseases","volume":"339","author":"RP Boot-Handford","year":"2010","journal-title":"Cell Tissue Res"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1111\/j.1463-1326.2010.01273.x","article-title":"Molecular chaperones and substrate ubiquitination control the efficiency of endoplasmic reticulum-associated degradation","volume":"12","author":"JL Goeckeler","year":"2010","journal-title":"Diabetes Obes Metab"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1126\/science.287.5453.664","article-title":"Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1","volume":"287","author":"F Urano","year":"2000","journal-title":"Science"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"3864","DOI":"10.1128\/MCB.22.11.3864-3874.2002","article-title":"The PERK eukaryotic initiation factor 2 alpha kinase is required for the development of the skeletal system, postnatal growth, and the function and viability of the pancreas","volume":"22","author":"PC Zhang","year":"2002","journal-title":"Mol Cell Biol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/S0092-8674(04)00344-7","article-title":"ATF4 is a substrate of RSK2 and an essential regulator of osteoblast biology: Implication for Coffin-Lowry syndrome","volume":"117","author":"XG Yang","year":"2004","journal-title":"Cell"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1083\/jcb.200708092","article-title":"Site-1 protease is essential for endochondral bone formation in mice","volume":"179","author":"D Patra","year":"2007","journal-title":"J Cell Biol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1002\/jcp.21543","article-title":"PERK Is Essential for Neonatal Skeletal Development to Regulate Osteoblast Proliferation and Differentiation","volume":"217","author":"J Wei","year":"2008","journal-title":"J Cell Physiol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"17020","DOI":"10.1074\/jbc.M802466200","article-title":"Endoplasmic reticulum (ER) chaperone regulation and survival of cells compensating for deficiency in the ER stress response kinase, PERK","volume":"283","author":"Y Yamaguchi","year":"2008","journal-title":"J Biol Chem"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"4809","DOI":"10.1074\/jbc.M110.152900","article-title":"Endoplasmic Reticulum Stress Response Mediated by the PERK-eIF2 alpha-ATF4 Pathway Is Involved in Osteoblast Differentiation Induced by BMP2","volume":"286","author":"A Saito","year":"2011","journal-title":"J Biol Chem"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1038\/ncb1962","article-title":"Regulation of endoplasmic reticulum stress response by a BBF2H7-mediated Sec23a pathway is essential for chondrogenesis","volume":"11","author":"A Saito","year":"2009","journal-title":"Nat Cell Biol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.biocel.2007.06.009","article-title":"Endochondral ossification: How cartilage is converted into bone in the developing skeleton","volume":"40","author":"EJ Mackie","year":"2008","journal-title":"Int J Biochem Cell Biol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1530\/JOE-11-0048","article-title":"The skeleton: a multi-functional complex organ. The growth plate chondrocyte and endochondral ossification","volume":"211","author":"EJ Mackie","year":"2011","journal-title":"J Endocrinol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"a008334","DOI":"10.1101\/cshperspect.a008334","article-title":"Development of the Endochondral Skeleton","volume":"5","author":"F Long","year":"2013","journal-title":"Cold Spring Harb Perspect Biol 2013"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1002\/ajmg.10828","article-title":"International Nosology and Classification of Constitutional Disorders of Bone (2001)","volume":"113","author":"CM Hall","year":"2002","journal-title":"Am J Med Genet"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1034\/j.1399-0004.2003.00046.x","article-title":"Skeletal dysplasias caused by a disruption of skeletal patterning and endochondral ossification","volume":"63","author":"B Newman","year":"2003","journal-title":"Clin Genet"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1002\/ajmg.a.33909","article-title":"Nosology and Classification of Genetic Skeletal Disorders: 2010 Revision","volume":"155A","author":"ML Warman","year":"2011","journal-title":"Am J Med Genet A"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1002\/humu.10066","article-title":"Pseudoachondroplasia and multiple epiphyseal dysplasia: Mutation review, molecular interactions, and genotype to phenotype correlations","volume":"19","author":"MD Briggs","year":"2002","journal-title":"Hum Mutat"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1371\/journal.pbio.0050044","article-title":"Surviving endoplasmic reticulum stress is coupled to altered chondrocyte differentiation and function","volume":"5","author":"KY Tsang","year":"2007","journal-title":"Plos Biol"},{"issue":"10","key":"ref23","doi-asserted-by":"crossref","first-page":"p.e1000691","DOI":"10.1371\/journal.pgen.1000691","article-title":"Targeted induction of endoplasmic reticulum stress induces cartilage pathology","volume":"5","author":"MH Rajpar","year":"2009","journal-title":"PLoS Genet"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1093\/hmg\/ddm121","article-title":"Decreased chondrocyte proliferation and dysregulated apoptosis in the cartilage growth plate are key features of a murine model of epiphyseal dysplasia caused by a matn3 mutation","volume":"16","author":"MP Leighton","year":"2007","journal-title":"Hum Mol Genet"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"2072","DOI":"10.1093\/hmg\/ddm155","article-title":"Reduced cell proliferation and increased apoptosis are significant pathological mechanisms in a murine model of mild pseudoachondroplasia resulting from a mutation in the C-terminal domain of COMP","volume":"16","author":"KA Pirog-Garcia","year":"2007","journal-title":"Hum Mol Genet"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1007\/s12192-010-0193-y","article-title":"An unfolded protein response is the initial cellular response to the expression of mutant matrilin-3 in a mouse model of multiple epiphyseal dysplasia","volume":"15","author":"S Nundlall","year":"2010","journal-title":"Cell Stress Chaperones"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1007\/s00335-011-9329-3","article-title":"ENU-induced missense mutation in the C-propeptide coding region of Col2a1 creates a mouse model of platyspondylic lethal skeletal dysplasia, Torrance type","volume":"22","author":"T Furuichi","year":"2011","journal-title":"Mamm Genome"},{"issue":"1","key":"ref28","doi-asserted-by":"crossref","first-page":"e86894","DOI":"10.1371\/journal.pone.0086894","article-title":"Endoplasmic Reticulum Stress-Unfolding Protein Response-Apoptosis Cascade Causes Chondrodysplasia in a col2a1 p.Gly1170Ser Mutated Mouse Model","volume":"9","author":"G Liang","year":"2014","journal-title":"PLoS ONE"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1002\/dvdy.24131","article-title":"Mechanisms and models of endoplasmic reticulum stress in chondrodysplasia","volume":"243","author":"SE Patterson","year":"2014","journal-title":"Dev. Dynam."},{"key":"ref30","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/S0945-053X(00)00122-0","article-title":"Stage-and tissue-specific expression of a Col2a1-Cre fusion gene in transgenic mice","volume":"19","author":"K Sakai","year":"2001","journal-title":"Matrix Biol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1083\/jcb.133.3.517","article-title":"An endoplasmic reticulum storage disease causing congenital goiter with hypothyroidism","volume":"133","author":"PS Kim","year":"1996","journal-title":"J Cell Biol"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"9909","DOI":"10.1073\/pnas.95.17.9909","article-title":"A single amino acid change in the acetylcholinesterase-like domain of thyroglobulin causes congenital goiter with hypothyroidism in the cog\/cog mouse: A model of human endoplasmic reticulum storage diseases","volume":"95","author":"PS Kim","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"9","key":"ref33","doi-asserted-by":"crossref","first-page":"e24600","DOI":"10.1371\/journal.pone.0024600","article-title":"Transcriptional profiling of chondrodysplasia growth plate cartilage reveals adaptive ER-stress networks that allow survival but disrupt hypertrophy","volume":"6","author":"TL Cameron","year":"2011","journal-title":"PLoS ONE"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1007\/s00018-007-7485-0","article-title":"Model systems for studying skeletal dysplasias caused by TSP-5\/COMP mutations","volume":"65","author":"KL Posey","year":"2008","journal-title":"Cell Mol Life Sci"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.matbio.2007.08.001","article-title":"Transgenic mice expressing D469 Delta mutated cartilage oligomeric matrix protein (COMP) show growth plate abnormalities and sternal malformations","volume":"27","author":"M Schmitz","year":"2008","journal-title":"Matrix Biol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.2353\/ajpath.2009.090184","article-title":"An Inducible Cartilage Oligomeric Matrix Protein Mouse Model Recapitulates Human Pseudoachondroplasia Phenotype","volume":"175","author":"KL Posey","year":"2009","journal-title":"Am J Pathol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1002\/humu.21631","article-title":"A novel form of chondrocyte stress is triggered by a COMP mutation causing Pseudoachondrodysplasia","volume":"33","author":"F Suleman","year":"2012","journal-title":"Hum Mutat"},{"issue":"10","key":"ref38","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1369\/0022155412458436","article-title":"Hypertrophic chondrocytes have a limited capacity to cope with increases in endoplasmic reticulum stress without triggering the unfolded protein response","volume":"60","author":"LHW Kung","year":"2012","journal-title":"J Histochem Cytochem"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1242\/bio.20135280","article-title":"Analysis of the cartilage proteome from three different mouse models of genetic skeletal diseases reveals common and discrete disease signatures","volume":"2","author":"PA Bell","year":"2013","journal-title":"Biology Ope"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1242\/dmm.013342","article-title":"A novel transgenic mouse model of growth plate dysplasia reveals that decreased chondrocyte proliferation due to chronic ER stress is a key factor in reduced bone growth","volume":"6","author":"B Gualeni","year":"2013","journal-title":"Dis Model Mech"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1002\/jemt.1070280606","article-title":"Mechanism of Longitudinal Bone-Growth and Its Regulation by Growth-Plate Chondrocytes","volume":"28","author":"EB Hunziker","year":"1994","journal-title":"Microsc Res Tech"},{"issue":"2","key":"ref42","doi-asserted-by":"crossref","first-page":"e85145","DOI":"10.1371\/journal.pone.0085145","article-title":"Abnormal Chondrocyte Apoptosis in the Cartilage Growth Plate is Influenced by Genetic Background and Deletion of CHOP in a Targeted Mouse Model of Pseudoachondroplasia","volume":"9","author":"KA Pirog","year":"2014","journal-title":"PLoS ONE"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0117016","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,23]],"date-time":"2018-10-23T03:26:20Z","timestamp":1540265180000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0117016"}},"subtitle":[],"editor":[{"given":"Florence","family":"Ruggiero","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2015,2,18]]},"references-count":42,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2015,2,18]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0117016","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,2,18]]}}}