Aggrecan turnover in human intervertebral disc as determined by the racemization of aspartic acid.
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, k(i), 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/L(Asp) 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.
Sivan
Sarit S
SS
Department of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel. Electronic address: sarit@bm.technion.ac.il.
Tsitron
Eve
E
Department of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel.
Wachtel
Ellen
E
Faculty of Chemistry, Weizmann Institute of Science, 76100, Rehovot, Israel.
Roughley
Peter J
PJ
Shriners Hospital for Children, Genetics Unit, Montreal, Quebec, H3G 1A6, Canada.
Sakkee
Nico
N
TNO Quality of Life, Business Unit Biomedical Research, P. O. Box 2215, 2301 CE Leiden, The Netherlands, and the.
van der Ham
Frits
F
TNO Quality of Life, Business Unit Biomedical Research, P. O. Box 2215, 2301 CE Leiden, The Netherlands, and the.
DeGroot
Jeroen
J
TNO Quality of Life, Business Unit Biomedical Research, P. O. Box 2215, 2301 CE Leiden, The Netherlands, and the.
Roberts
Sally
S
Centre for Spinal Studies, Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, Shropshire, SY10 7AG, United Kingdom.
Maroudas
Alice
A
Department of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053674:Aggrecans; D000375:Aging / Q000378:metabolism; D001224:Aspartic Acid / Q000032:analysis* / Q000737:chemistry*; D015415:Biomarkers / Q000032:analysis / Q000737:chemistry; D002648:Child; D002675:Child, Preschool; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007403:Intervertebral Disc / Q000378:metabolism*; D037181:Lectins, C-Type / Q000378:metabolism*; D008875:Middle Aged; D013122:Spinal Diseases / Q000378:metabolism; D013997:Time Factors
D053674:Aggrecans; D015415:Biomarkers; D011508:Chondroitin Sulfate Proteoglycans; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D001224:Aspartic Acid