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Article: Label-free quantitative proteomics reveals survival mechanisms developed by hypertrophic chondrocytes under ER stress

TitleLabel-free quantitative proteomics reveals survival mechanisms developed by hypertrophic chondrocytes under ER stress
Authors
Issue Date2016
PublisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/journals/jprobs
Citation
Journal of Proteome Research, 2016, v. 15 n. 1, p. 86-99 How to Cite?
AbstractEmerging evidence implicates ER stress caused by unfolded mutant proteins in chondrocytes as the underlying pathology of chondrodysplasias. ER stress is triggered in hypertrophic chondrocytes (HCs) in a mouse model (13del) of metaphyseal chondrodysplasia type Schmid (MCDS) caused by misfolded mutant collagen X proteins, but the HCs do not undergo apoptosis, rather chondrocyte differentiation is altered causing skeletal abnormality. How 13del HCs can escape from apoptosis and survive ER stress is not understood. Here, we compared the proteomes of HCs isolated from 13del growth plates with normal HCs, using label-free quantitative mass spectrometry approach. Pathway enrichment analyses of differentially expressed proteins showed significant changes in glycolysis and ER-mitochondria pathways in 13del HCs, as well as in ATDC5 cell lines expressing wt and 13del collagen X. In vivo, we showed expression of mitochondrial calcium channels was reduced while mitochondrial membrane polarity was maintained in 13del chondrocytes, while in vitro, glucose uptake was maintained. We propose 13del HCs survive by a mechanism whereby changes in ER-mitochondria communication reduce import of calcium coupled with maintenance of mitochondrial membrane polarity. These findings provide the initial insights to our understanding of growth plate changes caused by protein misfolding in the pathogenesis of chondrodysplasias
Persistent Identifierhttp://hdl.handle.net/10722/221882
ISSN
2015 Impact Factor: 4.173
2015 SCImago Journal Rankings: 1.962

 

DC FieldValueLanguage
dc.contributor.authorKudelko, MA-
dc.contributor.authorChan, CWL-
dc.contributor.authorSharma, RAKESH-
dc.contributor.authorYao, Q-
dc.contributor.authorLau, E-
dc.contributor.authorChu, IK-
dc.contributor.authorCheah, KSE-
dc.contributor.authorTanner, JA-
dc.contributor.authorChan, D-
dc.date.accessioned2015-12-21T05:46:28Z-
dc.date.available2015-12-21T05:46:28Z-
dc.date.issued2016-
dc.identifier.citationJournal of Proteome Research, 2016, v. 15 n. 1, p. 86-99-
dc.identifier.issn1535-3893-
dc.identifier.urihttp://hdl.handle.net/10722/221882-
dc.description.abstractEmerging evidence implicates ER stress caused by unfolded mutant proteins in chondrocytes as the underlying pathology of chondrodysplasias. ER stress is triggered in hypertrophic chondrocytes (HCs) in a mouse model (13del) of metaphyseal chondrodysplasia type Schmid (MCDS) caused by misfolded mutant collagen X proteins, but the HCs do not undergo apoptosis, rather chondrocyte differentiation is altered causing skeletal abnormality. How 13del HCs can escape from apoptosis and survive ER stress is not understood. Here, we compared the proteomes of HCs isolated from 13del growth plates with normal HCs, using label-free quantitative mass spectrometry approach. Pathway enrichment analyses of differentially expressed proteins showed significant changes in glycolysis and ER-mitochondria pathways in 13del HCs, as well as in ATDC5 cell lines expressing wt and 13del collagen X. In vivo, we showed expression of mitochondrial calcium channels was reduced while mitochondrial membrane polarity was maintained in 13del chondrocytes, while in vitro, glucose uptake was maintained. We propose 13del HCs survive by a mechanism whereby changes in ER-mitochondria communication reduce import of calcium coupled with maintenance of mitochondrial membrane polarity. These findings provide the initial insights to our understanding of growth plate changes caused by protein misfolding in the pathogenesis of chondrodysplasias-
dc.languageeng-
dc.publisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/journals/jprobs-
dc.relation.ispartofJournal of Proteome Research-
dc.titleLabel-free quantitative proteomics reveals survival mechanisms developed by hypertrophic chondrocytes under ER stress-
dc.typeArticle-
dc.identifier.emailChu, IK: ivankchu@hkucc.hku.hk-
dc.identifier.emailCheah, KSE: hrmbdkc@hku.hk-
dc.identifier.emailTanner, JA: jatanner@hkucc.hku.hk-
dc.identifier.emailChan, D: chand@hku.hk-
dc.identifier.authorityChu, IK=rp00683-
dc.identifier.authorityCheah, KSE=rp00342-
dc.identifier.authorityTanner, JA=rp00495-
dc.identifier.authorityChan, D=rp00540-
dc.identifier.doi10.1021/acs.jproteome.5b00537-
dc.identifier.pmid26587667-
dc.identifier.hkuros256369-
dc.identifier.volume15-
dc.identifier.issue1-
dc.identifier.spage86-
dc.identifier.epage99-
dc.publisher.placeUnited States-

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