File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Collagen II is essential for the removal of the notochord and the formation of intervertebral discs

TitleCollagen II is essential for the removal of the notochord and the formation of intervertebral discs
Authors
Issue Date1998
PublisherRockefeller University Press. The Journal's web site is located at http://www.jcb.org
Citation
Journal Of Cell Biology, 1998, v. 143 n. 5, p. 1399-1412 How to Cite?
AbstractCollagen II is a fibril-forming collagen that is mainly expressed in cartilage. Collagen II-deficient mice produce structurally abnormal cartilage that lacks growth plates in long bones, and as a result these mice develop a skeleton without endochondral bone formation. Here, we report that Col2a1- null mice are unable to dismantle the notochord. This defect is associated with the inability to develop intervertebral discs (IVDs). During normal embryogenesis, the nucleus pulposus of future IVDs forms from regional expansion of the notochord, which is simultaneously dismantled in the region of the developing vertebral bodies. However, in Col2a1-null mice, the notochord is not removed in the vertebral bodies and persists as a rod-like structure until birth. It has been suggested that this regional notochordal degeneration results from changes in cell death and proliferation. Our experiments with wildtype mice showed that differential proliferation and apoptosis play no role in notochordal reorganization. An alternative hypothesis is that the cartilage matrix exerts mechanical forces that induce notochord removal. Several of our findings support this hypothesis. Immunohistological analyses, in situ hybridization, and biochemical analyses demonstrate that collagens I and III are ectopically expressed in Col2a1- null cartilage. Assembly of the abnormal collagens into a mature insoluble matrix is retarded and collagen fibrils are sparse, disorganized, and irregular. We propose that this disorganized abnormal cartilage collagen matrix is structurally weakened and is unable to constrain proteoglycan- induced osmotic swelling pressure. The accumulation of fluid leads to tissue enlargement and a reduction in the internal swelling pressure. These changes may be responsible for the abnormal notochord removal in Col2a1-null mice. Our studies also show that chondrocytes do not need a collagen II environment to express cartilage-specific matrix components and to hypertrophy. Furthermore, biochemical analysis of collagen XI in mutant cartilage showed that α1(XI) and α2(XI) chains form unstable collagen XI molecules, demonstrating that the α3(XI) chain, which is an alternative, posttranslationally modified form of the Col2a1 gene, is essential for assembly and stability of triple helical collagen XI.
Persistent Identifierhttp://hdl.handle.net/10722/68198
ISSN
2015 Impact Factor: 8.717
2015 SCImago Journal Rankings: 7.923
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorAszódi, Aen_HK
dc.contributor.authorChan, Den_HK
dc.contributor.authorHunziker, Een_HK
dc.contributor.authorBateman, JFen_HK
dc.contributor.authorFässler, Ren_HK
dc.date.accessioned2010-09-06T06:02:17Z-
dc.date.available2010-09-06T06:02:17Z-
dc.date.issued1998en_HK
dc.identifier.citationJournal Of Cell Biology, 1998, v. 143 n. 5, p. 1399-1412en_HK
dc.identifier.issn0021-9525en_HK
dc.identifier.urihttp://hdl.handle.net/10722/68198-
dc.description.abstractCollagen II is a fibril-forming collagen that is mainly expressed in cartilage. Collagen II-deficient mice produce structurally abnormal cartilage that lacks growth plates in long bones, and as a result these mice develop a skeleton without endochondral bone formation. Here, we report that Col2a1- null mice are unable to dismantle the notochord. This defect is associated with the inability to develop intervertebral discs (IVDs). During normal embryogenesis, the nucleus pulposus of future IVDs forms from regional expansion of the notochord, which is simultaneously dismantled in the region of the developing vertebral bodies. However, in Col2a1-null mice, the notochord is not removed in the vertebral bodies and persists as a rod-like structure until birth. It has been suggested that this regional notochordal degeneration results from changes in cell death and proliferation. Our experiments with wildtype mice showed that differential proliferation and apoptosis play no role in notochordal reorganization. An alternative hypothesis is that the cartilage matrix exerts mechanical forces that induce notochord removal. Several of our findings support this hypothesis. Immunohistological analyses, in situ hybridization, and biochemical analyses demonstrate that collagens I and III are ectopically expressed in Col2a1- null cartilage. Assembly of the abnormal collagens into a mature insoluble matrix is retarded and collagen fibrils are sparse, disorganized, and irregular. We propose that this disorganized abnormal cartilage collagen matrix is structurally weakened and is unable to constrain proteoglycan- induced osmotic swelling pressure. The accumulation of fluid leads to tissue enlargement and a reduction in the internal swelling pressure. These changes may be responsible for the abnormal notochord removal in Col2a1-null mice. Our studies also show that chondrocytes do not need a collagen II environment to express cartilage-specific matrix components and to hypertrophy. Furthermore, biochemical analysis of collagen XI in mutant cartilage showed that α1(XI) and α2(XI) chains form unstable collagen XI molecules, demonstrating that the α3(XI) chain, which is an alternative, posttranslationally modified form of the Col2a1 gene, is essential for assembly and stability of triple helical collagen XI.en_HK
dc.languageengen_HK
dc.publisherRockefeller University Press. The Journal's web site is located at http://www.jcb.orgen_HK
dc.relation.ispartofJournal of Cell Biologyen_HK
dc.rightsThe Journal of Cell Biology. Copyright © Rockefeller University Press.en_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshBase Sequenceen_HK
dc.subject.meshBody Patterningen_HK
dc.subject.meshCartilage - metabolismen_HK
dc.subject.meshCell Differentiationen_HK
dc.subject.meshCell Divisionen_HK
dc.subject.meshCells, Cultureden_HK
dc.subject.meshChondrocytes - metabolismen_HK
dc.subject.meshCollagen - deficiency - genetics - metabolismen_HK
dc.subject.meshDNA Primers - geneticsen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshImmunohistochemistryen_HK
dc.subject.meshIntervertebral Disc - embryology - metabolismen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMiceen_HK
dc.subject.meshMice, Knockouten_HK
dc.subject.meshModels, Biologicalen_HK
dc.subject.meshNotochord - cytology - embryology - metabolismen_HK
dc.subject.meshPregnancyen_HK
dc.subject.meshRNA, Messenger - genetics - metabolismen_HK
dc.titleCollagen II is essential for the removal of the notochord and the formation of intervertebral discsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0021-9525&volume=143&spage=1399&epage=1412&date=1998&atitle=Collagen+II+is+essential+for+the+removal+of+the+notochord+and+the+formation+of+intervertebral+discsen_HK
dc.identifier.emailChan, D:chand@hkucc.hku.hken_HK
dc.identifier.authorityChan, D=rp00540en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1083/jcb.143.5.1399en_HK
dc.identifier.pmid9832566en_HK
dc.identifier.scopuseid_2-s2.0-0032583171en_HK
dc.identifier.hkuros43078en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0032583171&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume143en_HK
dc.identifier.issue5en_HK
dc.identifier.spage1399en_HK
dc.identifier.epage1412en_HK
dc.identifier.isiWOS:000077398300023-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridAszódi, A=7005953487en_HK
dc.identifier.scopusauthoridChan, D=7402216545en_HK
dc.identifier.scopusauthoridHunziker, E=7006730591en_HK
dc.identifier.scopusauthoridBateman, JF=16135557700en_HK
dc.identifier.scopusauthoridFässler, R=35493223600en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats