Structure, function, aging and turnover of aggrecan in the intervertebral disc

Aggrecan is the major non-collagenous component of the intervertebral disc. It is a large proteoglycan possessing numerous glycosaminoglycan chains and the ability to form aggregates in association with hyaluronan. Its abundance and unique molecular features provide the disc with its osmotic propert...

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Veröffentlicht in:Biochimica et biophysica acta Jg. 1840; H. 10; S. 3181 - 3189
Hauptverfasser: Sivan, Sarit Sara, Wachtel, Ellen, Roughley, Peter
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Netherlands Elsevier B.V 01.10.2014
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ISSN:0304-4165, 0006-3002, 1872-8006
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Abstract Aggrecan is the major non-collagenous component of the intervertebral disc. It is a large proteoglycan possessing numerous glycosaminoglycan chains and the ability to form aggregates in association with hyaluronan. Its abundance and unique molecular features provide the disc with its osmotic properties and ability to withstand compressive loads. Degradation and loss of aggrecan result in impairment of disc function and the onset of degeneration. This review summarizes current knowledge concerning the structure and function of aggrecan in the normal intervertebral disc and how and why these change in aging and degenerative disc disease. It also outlines how supplementation with aggrecan or a biomimetic may be of therapeutic value in treating the degenerate disc. Aggrecan abundance reaches a plateau in the early twenties, declining thereafter due to proteolysis, mainly by matrix metalloproteinases and aggrecanases, though degradation of hyaluronan and non-enzymic glycation may also participate. Aggrecan loss is an early event in disc degeneration, although it is a lengthy process as degradation products may accumulate in the disc for decades. The low turnover rate of the remaining aggrecan is an additional contributing factor, preventing protein renewal. It may be possible to retard the degenerative process by restoring the aggrecan content of the disc, or by supplementing with a bioimimetic possessing similar osmotic properties. This review provides a basis for scientists and clinicians to understand and appreciate the central role of aggrecan in the function, degeneration and repair of the intervertebral disc. •Aggrecan abundance reaches a plateau in the early twenties, then slowly declines.•Aggrecan abundance declines due to proteolysis, mainly by MMPs and aggrecanases.•Aggrecan loss is an early event in disc degeneration.•The low turnover rate of the degraded aggrecan prevents its replacement.•Aggrecan restoration or bioimimetic supplementation may retard disc degeneration.
AbstractList Aggrecan is the major non-collagenous component of the intervertebral disc. It is a large proteoglycan possessing numerous glycosaminoglycan chains and the ability to form aggregates in association with hyaluronan. Its abundance and unique molecular features provide the disc with its osmotic properties and ability to withstand compressive loads. Degradation and loss of aggrecan result in impairment of disc function and the onset of degeneration.BACKGROUNDAggrecan is the major non-collagenous component of the intervertebral disc. It is a large proteoglycan possessing numerous glycosaminoglycan chains and the ability to form aggregates in association with hyaluronan. Its abundance and unique molecular features provide the disc with its osmotic properties and ability to withstand compressive loads. Degradation and loss of aggrecan result in impairment of disc function and the onset of degeneration.This review summarizes current knowledge concerning the structure and function of aggrecan in the normal intervertebral disc and how and why these change in aging and degenerative disc disease. It also outlines how supplementation with aggrecan or a biomimetic may be of therapeutic value in treating the degenerate disc.SCOPE OF REVIEWThis review summarizes current knowledge concerning the structure and function of aggrecan in the normal intervertebral disc and how and why these change in aging and degenerative disc disease. It also outlines how supplementation with aggrecan or a biomimetic may be of therapeutic value in treating the degenerate disc.Aggrecan abundance reaches a plateau in the early twenties, declining thereafter due to proteolysis, mainly by matrix metalloproteinases and aggrecanases, though degradation of hyaluronan and non-enzymic glycation may also participate. Aggrecan loss is an early event in disc degeneration, although it is a lengthy process as degradation products may accumulate in the disc for decades. The low turnover rate of the remaining aggrecan is an additional contributing factor, preventing protein renewal. It may be possible to retard the degenerative process by restoring the aggrecan content of the disc, or by supplementing with a bioimimetic possessing similar osmotic properties.MAJOR CONCLUSIONSAggrecan abundance reaches a plateau in the early twenties, declining thereafter due to proteolysis, mainly by matrix metalloproteinases and aggrecanases, though degradation of hyaluronan and non-enzymic glycation may also participate. Aggrecan loss is an early event in disc degeneration, although it is a lengthy process as degradation products may accumulate in the disc for decades. The low turnover rate of the remaining aggrecan is an additional contributing factor, preventing protein renewal. It may be possible to retard the degenerative process by restoring the aggrecan content of the disc, or by supplementing with a bioimimetic possessing similar osmotic properties.This review provides a basis for scientists and clinicians to understand and appreciate the central role of aggrecan in the function, degeneration and repair of the intervertebral disc.GENERAL SIGNIFICANCEThis review provides a basis for scientists and clinicians to understand and appreciate the central role of aggrecan in the function, degeneration and repair of the intervertebral disc.
Aggrecan is the major non-collagenous component of the intervertebral disc. It is a large proteoglycan possessing numerous glycosaminoglycan chains and the ability to form aggregates in association with hyaluronan. Its abundance and unique molecular features provide the disc with its osmotic properties and ability to withstand compressive loads. Degradation and loss of aggrecan result in impairment of disc function and the onset of degeneration. This review summarizes current knowledge concerning the structure and function of aggrecan in the normal intervertebral disc and how and why these change in aging and degenerative disc disease. It also outlines how supplementation with aggrecan or a biomimetic may be of therapeutic value in treating the degenerate disc. Aggrecan abundance reaches a plateau in the early twenties, declining thereafter due to proteolysis, mainly by matrix metalloproteinases and aggrecanases, though degradation of hyaluronan and non-enzymic glycation may also participate. Aggrecan loss is an early event in disc degeneration, although it is a lengthy process as degradation products may accumulate in the disc for decades. The low turnover rate of the remaining aggrecan is an additional contributing factor, preventing protein renewal. It may be possible to retard the degenerative process by restoring the aggrecan content of the disc, or by supplementing with a bioimimetic possessing similar osmotic properties. This review provides a basis for scientists and clinicians to understand and appreciate the central role of aggrecan in the function, degeneration and repair of the intervertebral disc. •Aggrecan abundance reaches a plateau in the early twenties, then slowly declines.•Aggrecan abundance declines due to proteolysis, mainly by MMPs and aggrecanases.•Aggrecan loss is an early event in disc degeneration.•The low turnover rate of the degraded aggrecan prevents its replacement.•Aggrecan restoration or bioimimetic supplementation may retard disc degeneration.
Aggrecan is the major non-collagenous component of the intervertebral disc. It is a large proteoglycan possessing numerous glycosaminoglycan chains and the ability to form aggregates in association with hyaluronan. Its abundance and unique molecular features provide the disc with its osmotic properties and ability to withstand compressive loads. Degradation and loss of aggrecan result in impairment of disc function and the onset of degeneration.This review summarizes current knowledge concerning the structure and function of aggrecan in the normal intervertebral disc and how and why these change in aging and degenerative disc disease. It also outlines how supplementation with aggrecan or a biomimetic may be of therapeutic value in treating the degenerate disc.Aggrecan abundance reaches a plateau in the early twenties, declining thereafter due to proteolysis, mainly by matrix metalloproteinases and aggrecanases, though degradation of hyaluronan and non-enzymic glycation may also participate. Aggrecan loss is an early event in disc degeneration, although it is a lengthy process as degradation products may accumulate in the disc for decades. The low turnover rate of the remaining aggrecan is an additional contributing factor, preventing protein renewal. It may be possible to retard the degenerative process by restoring the aggrecan content of the disc, or by supplementing with a bioimimetic possessing similar osmotic properties.This review provides a basis for scientists and clinicians to understand and appreciate the central role of aggrecan in the function, degeneration and repair of the intervertebral disc.
Aggrecan is the major non-collagenous component of the intervertebral disc. It is a large proteoglycan possessing numerous glycosaminoglycan chains and the ability to form aggregates in association with hyaluronan. Its abundance and unique molecular features provide the disc with its osmotic properties and ability to withstand compressive loads. Degradation and loss of aggrecan result in impairment of disc function and the onset of degeneration. This review summarizes current knowledge concerning the structure and function of aggrecan in the normal intervertebral disc and how and why these change in aging and degenerative disc disease. It also outlines how supplementation with aggrecan or a biomimetic may be of therapeutic value in treating the degenerate disc. Aggrecan abundance reaches a plateau in the early twenties, declining thereafter due to proteolysis, mainly by matrix metalloproteinases and aggrecanases, though degradation of hyaluronan and non-enzymic glycation may also participate. Aggrecan loss is an early event in disc degeneration, although it is a lengthy process as degradation products may accumulate in the disc for decades. The low turnover rate of the remaining aggrecan is an additional contributing factor, preventing protein renewal. It may be possible to retard the degenerative process by restoring the aggrecan content of the disc, or by supplementing with a bioimimetic possessing similar osmotic properties. This review provides a basis for scientists and clinicians to understand and appreciate the central role of aggrecan in the function, degeneration and repair of the intervertebral disc.
Author Wachtel, Ellen
Roughley, Peter
Sivan, Sarit Sara
Author_xml – sequence: 1
  givenname: Sarit Sara
  surname: Sivan
  fullname: Sivan, Sarit Sara
  email: ssivan@braude.ac.il
  organization: Department of Biotechnology Engineering, ORT Braude College, Karmiel 21982 Israel
– sequence: 2
  givenname: Ellen
  surname: Wachtel
  fullname: Wachtel, Ellen
  organization: Faculty of Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
– sequence: 3
  givenname: Peter
  surname: Roughley
  fullname: Roughley, Peter
  organization: Shriners Hospital for Children, Genetics Unit, 1529 Cedar Avenue, Montreal, Quebec H3G 1A6, Canada
BackLink https://www.ncbi.nlm.nih.gov/pubmed/25065289$$D View this record in MEDLINE/PubMed
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ISICitedReferencesCount 152
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ISSN 0304-4165
0006-3002
IngestDate Sun Sep 28 09:07:55 EDT 2025
Wed Oct 01 14:50:46 EDT 2025
Thu Apr 03 07:09:03 EDT 2025
Sat Nov 29 01:38:00 EST 2025
Tue Nov 18 22:19:00 EST 2025
Fri Feb 23 02:32:43 EST 2024
IsPeerReviewed true
IsScholarly true
Issue 10
Keywords CRP
NP
TNFα
ADAMTS
Biomimetics
Intervertebral disc
HYALs
Turnover
Degeneration
Repair
Asp
CML
EGF
AF
IGD
MMPs
KS
OSM
AGEs
CEL
GAG
BMP7
GDF5
ECM
IL1
CS
IVD
TGFβ
HA
Aggrecan
Language English
License Copyright © 2014 Elsevier B.V. All rights reserved.
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PMID 25065289
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PQPubID 23479
PageCount 9
ParticipantIDs proquest_miscellaneous_2000214484
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pubmed_primary_25065289
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PublicationCentury 2000
PublicationDate 2014-10-01
PublicationDateYYYYMMDD 2014-10-01
PublicationDate_xml – month: 10
  year: 2014
  text: 2014-10-01
  day: 01
PublicationDecade 2010
PublicationPlace Netherlands
PublicationPlace_xml – name: Netherlands
PublicationTitle Biochimica et biophysica acta
PublicationTitleAlternate Biochim Biophys Acta
PublicationYear 2014
Publisher Elsevier B.V
Publisher_xml – name: Elsevier B.V
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Snippet Aggrecan is the major non-collagenous component of the intervertebral disc. It is a large proteoglycan possessing numerous glycosaminoglycan chains and the...
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SubjectTerms Aggrecan
Aggrecans - metabolism
Aging - metabolism
Aging - pathology
Animals
Biomimetics
Degeneration
glycation
Humans
hyaluronic acid
Intervertebral disc
Intervertebral Disc - metabolism
Intervertebral Disc - pathology
Intervertebral Disc Degeneration - metabolism
Intervertebral Disc Degeneration - pathology
intervertebral disks
metalloproteinases
proteoglycans
proteolysis
Repair
scientists
Structure-Activity Relationship
Turnover
Title Structure, function, aging and turnover of aggrecan in the intervertebral disc
URI https://dx.doi.org/10.1016/j.bbagen.2014.07.013
https://www.ncbi.nlm.nih.gov/pubmed/25065289
https://www.proquest.com/docview/1566402779
https://www.proquest.com/docview/2000214484
Volume 1840
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