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Aggrecan turnover in human intervertebral disc as determined by the racemization of aspartic acid

Author: Sivan, S.S. · Tsitron, E. · Wachtel, E. · Roughley, P.J. · Sakkee, N. · Ham, F. van der · Groot, J.de · Roberts, S. · Maroudas, A.
Type:article
Date:2006
Institution: TNO Kwaliteit van Leven
Source:Journal of Biological Chemistry, 19, 281, 13009-13014
Identifier: 239270
doi: doi:10.1074/jbc.M600296200
Keywords: Biology · Biomedical Research · Agglomeration · Buoyancy · Cartilage · Synthesis (chemical) · Tissue · Aspartic acid · Non-aggregating molecules · Non-aggregating proteoglycans · Racemization · Organic acids · Aggrecan · Hyaluronic acid · Proteoglycan · Articular cartilage · Controlled study · Human · Human tissue · Racemization · Turnover time · Adolescent · Adult · Aged · Aged, 80 and over · Aggrecans · Aging · Aspartic Acid · Biological Markers · Child · Child, Preschool · Extracellular Matrix Proteins · Humans · Infant · Infant, Newborn · Intervertebral Disk · Lectins, C-Type · Middle Aged · Proteochondroitin Sulfates · Spinal Diseases · Time Factors

Abstract

We have used the racemization of aspartic acid as a marker for the "molecular age" of aggrecan components of the human intervertebral disc matrix (aggregating and non-aggregating proteoglycans as well as the different buoyant density fractions of aggrecan). By measuring the D/L Asp ratio of the various aggrecan species as a function of age and using the values of the racemization constant, ki, found earlier for aggrecan in articular cartilage, we were able to establish directly the relative residence time of these molecules in human intervertebral disc matrix. For A1 preparations taken from normal tissue, turnover rates of 0.059 ± 0.01 and 0.063 ± 0.01/year correspond to half-life values of 12 ± 2.0 and 11.23 ± 1.9 years for nucleus pulposus and annulus fibrosus, respectively; the turnover rates of 0.084 ± 0.022 and 0.092 ± 0.034/year for degenerate tissue correspond to half-life values of 8.77 ± 2.2 and 8.41 ± 2.8 years, suggesting increased rate of removal of small aggrecan fragments. For the large monomer, fraction A1D1, turnover is 0.13 ± 0.04/year, corresponding to a half-life of 5.56 ± 1.58 years, similar to 3.4 years in human articular cartilage. For the binding region (A1D6), turnover is 0.033 ± 0.0012/year, corresponding to a half-life of 21.53 ± 0.6 years, similar to 23.5 years in articular cartilage. A1 preparations from nucleus pulposus contain a lower proportion of aggregating proteoglycans as compared with annulus fibrosus, suggesting increased proteolytic modification in the nucleus pulposus. D/LAsp values in aggregating and non-aggregating proteoglycans of a 24-year-old individual show similar results, suggesting that the non-aggregating molecules are synthesized initially as aggregating proteoglycans, which thereafter undergo cleavage and detachment from hyaluronan. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc. Chemicals / CAS: aspartic acid, 56-84-8, 6899-03-2; hyaluronic acid, 31799-91-4, 9004-61-9, 9067-32-7; Aggrecans; Aspartic Acid, 56-84-8; Biological Markers; Extracellular Matrix Proteins; Lectins, C-Type; Proteochondroitin Sulfates