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Article: Surviving endoplasmic reticulum stress is coupled to altered chondrocyte differentiation and function.

TitleSurviving endoplasmic reticulum stress is coupled to altered chondrocyte differentiation and function.
Authors
Issue Date2007
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosbiology.org/plosonline/?request=index-html
Citation
Plos Biology, 2007, v. 5 n. 3, p. e44 How to Cite?
AbstractIn protein folding and secretion disorders, activation of endoplasmic reticulum (ER) stress signaling (ERSS) protects cells, alleviating stress that would otherwise trigger apoptosis. Whether the stress-surviving cells resume normal function is not known. We studied the in vivo impact of ER stress in terminally differentiating hypertrophic chondrocytes (HCs) during endochondral bone formation. In transgenic mice expressing mutant collagen X as a consequence of a 13-base pair deletion in Col10a1 (13del), misfolded alpha1(X) chains accumulate in HCs and elicit ERSS. Histological and gene expression analyses showed that these chondrocytes survived ER stress, but terminal differentiation is interrupted, and endochondral bone formation is delayed, producing a chondrodysplasia phenotype. This altered differentiation involves cell-cycle re-entry, the re-expression of genes characteristic of a prehypertrophic-like state, and is cell-autonomous. Concomitantly, expression of Col10a1 and 13del mRNAs are reduced, and ER stress is alleviated. ERSS, abnormal chondrocyte differentiation, and altered growth plate architecture also occur in mice expressing mutant collagen II and aggrecan. Alteration of the differentiation program in chondrocytes expressing unfolded or misfolded proteins may be part of an adaptive response that facilitates survival and recovery from the ensuing ER stress. However, the altered differentiation disrupts the highly coordinated events of endochondral ossification culminating in chondrodysplasia.
Persistent Identifierhttp://hdl.handle.net/10722/68148
ISSN
2015 Impact Factor: 8.668
2015 SCImago Journal Rankings: 5.293
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorTsang, KYen_HK
dc.contributor.authorChan, Den_HK
dc.contributor.authorCheslett, Den_HK
dc.contributor.authorChan, WCen_HK
dc.contributor.authorSo, CLen_HK
dc.contributor.authorMelhado, IGen_HK
dc.contributor.authorChan, TWen_HK
dc.contributor.authorKwan, KMen_HK
dc.contributor.authorHunziker, EBen_HK
dc.contributor.authorYamada, Yen_HK
dc.contributor.authorBateman, JFen_HK
dc.contributor.authorCheung, KMen_HK
dc.contributor.authorCheah, KSen_HK
dc.date.accessioned2010-09-06T06:01:49Z-
dc.date.available2010-09-06T06:01:49Z-
dc.date.issued2007en_HK
dc.identifier.citationPlos Biology, 2007, v. 5 n. 3, p. e44en_HK
dc.identifier.issn1545-7885en_HK
dc.identifier.urihttp://hdl.handle.net/10722/68148-
dc.description.abstractIn protein folding and secretion disorders, activation of endoplasmic reticulum (ER) stress signaling (ERSS) protects cells, alleviating stress that would otherwise trigger apoptosis. Whether the stress-surviving cells resume normal function is not known. We studied the in vivo impact of ER stress in terminally differentiating hypertrophic chondrocytes (HCs) during endochondral bone formation. In transgenic mice expressing mutant collagen X as a consequence of a 13-base pair deletion in Col10a1 (13del), misfolded alpha1(X) chains accumulate in HCs and elicit ERSS. Histological and gene expression analyses showed that these chondrocytes survived ER stress, but terminal differentiation is interrupted, and endochondral bone formation is delayed, producing a chondrodysplasia phenotype. This altered differentiation involves cell-cycle re-entry, the re-expression of genes characteristic of a prehypertrophic-like state, and is cell-autonomous. Concomitantly, expression of Col10a1 and 13del mRNAs are reduced, and ER stress is alleviated. ERSS, abnormal chondrocyte differentiation, and altered growth plate architecture also occur in mice expressing mutant collagen II and aggrecan. Alteration of the differentiation program in chondrocytes expressing unfolded or misfolded proteins may be part of an adaptive response that facilitates survival and recovery from the ensuing ER stress. However, the altered differentiation disrupts the highly coordinated events of endochondral ossification culminating in chondrodysplasia.en_HK
dc.languageengen_HK
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosbiology.org/plosonline/?request=index-htmlen_HK
dc.relation.ispartofPLoS biologyen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshCell Differentiation-
dc.subject.meshChondrocytes - cytology-
dc.subject.meshDNA Primers-
dc.subject.meshEndoplasmic Reticulum - metabolism-
dc.subject.meshMice, Transgenic-
dc.titleSurviving endoplasmic reticulum stress is coupled to altered chondrocyte differentiation and function.en_HK
dc.typeArticleen_HK
dc.identifier.emailChan, D:chand@hkucc.hku.hken_HK
dc.identifier.emailCheung, KM:cheungmc@hku.hken_HK
dc.identifier.emailCheah, KS:hrmbdkc@hku.hken_HK
dc.identifier.authorityChan, D=rp00540en_HK
dc.identifier.authorityCheung, KM=rp00387en_HK
dc.identifier.authorityCheah, KS=rp00342en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pbio.0050044en_HK
dc.identifier.pmid17298185-
dc.identifier.pmcidPMC1820825-
dc.identifier.scopuseid_2-s2.0-33947274572en_HK
dc.identifier.hkuros128886en_HK
dc.identifier.volume5en_HK
dc.identifier.issue3en_HK
dc.identifier.spagee44en_HK
dc.identifier.epagee44en_HK
dc.identifier.eissn1545-7885-
dc.identifier.isiWOS:000245243500016-
dc.identifier.f10001071131-
dc.identifier.scopusauthoridTsang, KY=22635904200en_HK
dc.identifier.scopusauthoridChan, D=7402216545en_HK
dc.identifier.scopusauthoridCheslett, D=16041327500en_HK
dc.identifier.scopusauthoridChan, WC=24545687600en_HK
dc.identifier.scopusauthoridSo, CL=36979763700en_HK
dc.identifier.scopusauthoridMelhado, IG=55006348100en_HK
dc.identifier.scopusauthoridChan, TW=34967926200en_HK
dc.identifier.scopusauthoridKwan, KM=7006405800en_HK
dc.identifier.scopusauthoridHunziker, EB=7006730591en_HK
dc.identifier.scopusauthoridYamada, Y=7407166140en_HK
dc.identifier.scopusauthoridBateman, JF=16135557700en_HK
dc.identifier.scopusauthoridCheung, KM=7402406754en_HK
dc.identifier.scopusauthoridCheah, KS=35387746200en_HK

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