Age-related changes in fibromodulin and lumican in human intervertebral discs.
METHODS
An analysis of proteoglycans of the intervertebral disc using immunoblotting of tissue extracts.


OBJECTIVE
To investigate the changes in structure and abundance of fibromodulin and lumican in human intervertebral discs during aging and degeneration.


BACKGROUND
Fibromodulin and lumican are keratan sulfate proteoglycan constituents of the disc's extracellular matrix, whose interaction with collagen fibrils may contribute to the mechanical properties of the tissue. Changes in their abundance and/or structure that occur with aging and degeneration therefore may have an impact on disc function.


METHODS
Lumbar intervertebral discs were obtained from individuals of different ages, and extracts of anulus fibrosus and nucleus pulposus were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting using antibodies specific for fibromodulin and lumican.


RESULTS
The major changes in abundance observed with age were a decrease in fibromodulin in the adult nucleus pulposus and an increase in lumican in anulus fibrosus during early juvenile development. In addition, fibromodulin in the anulus fibrosus exhibited a structural change with increasing age, characterized by a shift toward the predominance of its glycoprotein form lacking keratan sulfate. Fibromodulin was more abundant in the anulus fibrosus than in nucleus pulposus at all ages, whereas lumican was much more abundant in nucleus pulposus than in anulus fibrosus in the young juvenile; in the adult, however, lumican was present in comparable levels in both tissues. With increasing degrees of degeneration, fibromodulin exhibited an increase in abundance.


CONCLUSIONS
Growth, aging, and degeneration of the intervertebral disc are associated with changes in the abundance and structure of fibromodulin and lumican, which presumably influence the functional properties of the tissue.
Sztrolovics
R
R
Joint Diseases Laboratory, Shriners Hospital for Children, Montreal, Quebec, Canada.
Alini
M
M
Mort
J S
JS
Roughley
P J
PJ
D000293:Adolescent; D000328:Adult; D000375:Aging / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins; D000071235:Fibromodulin; D006801:Humans; D007223:Infant; D007403:Intervertebral Disc / Q000378:metabolism*; D007405:Intervertebral Disc Displacement / Q000378:metabolism / Q000473:pathology; D007632:Keratan Sulfate / Q000378:metabolism*; D000071234:Lumican; D008875:Middle Aged; D011509:Proteoglycans
D002352:Carrier Proteins; D011508:Chondroitin Sulfate Proteoglycans; D016326:Extracellular Matrix Proteins; C000604330:FMOD protein, human; C000604306:LUM protein, human; D000071234:Lumican; D011509:Proteoglycans; D000071235:Fibromodulin; D007632:Keratan Sulfate