Fragmentation of decorin, biglycan, lumican and keratocan is elevated in degenerate human meniscus, knee and hip articular cartilages compared with age-matched macroscopically normal and control tissues.
BACKGROUND
The small leucine-rich proteoglycans (SLRPs) modulate tissue organization, cellular proliferation, matrix adhesion, growth factor and cytokine responses, and sterically protect the surface of collagen type I and II fibrils from proteolysis. Catabolism of SLRPs has important consequences for the integrity of articular cartilage and meniscus by interfering with their tissue homeostatic functions.


METHODS
SLRPs were dissociatively extracted from articular cartilage from total knee and hip replacements, menisci from total knee replacements, macroscopically normal and fibrillated knee articular cartilage from mature age-matched donors, and normal young articular cartilage. The tissue extracts were digested with chondroitinase ABC and keratanase-I before identification of SLRP core protein species by Western blotting using antibodies to the carboxyl-termini of the SLRPs.


RESULTS
Multiple core-protein species were detected for all of the SLRPs (except fibromodulin) in the degenerate osteoarthritic articular cartilage and menisci. Fibromodulin had markedly less fragments detected with the carboxyl-terminal antibody compared with other SLRPs. There were fewer SLRP catabolites in osteoarthritic hip than in knee articular cartilage. Fragmentation of all SLRPs in normal age-matched, nonfibrillated knee articular cartilage was less than in fibrillated articular cartilage from the same knee joint or total knee replacement articular cartilage specimens of similar age. There was little fragmentation of SLRPs in normal control knee articular cartilage. Only decorin exhibited a consistent increase in fragmentation in menisci in association with osteoarthritis. There were no fragments of decorin, biglycan, lumican, or keratocan that were unique to any tissue. A single fibromodulin fragment was detected in osteoarthritic articular cartilage but not meniscus. All SLRPs showed a modest age-related increase in fragmentation in knee articular and meniscal cartilage but not in other tissues.


CONCLUSIONS
Enhanced fragmentation of SLRPs is evident in degenerate articular cartilage and meniscus. Specific decorin and fibromodulin core protein fragments in degenerate meniscus and/or human articular cartilage may be of value as biomarkers of disease. Once the enzymes responsible for their generation have been identified, further research may identify them as therapeutic targets.
Melrose
James
J
Raymond Purves Research Laboratory, Institute of Bone & Joint Research, Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, Leonards, NSW, Australia. jmelrose@med.usyd.edu.au
Fuller
Emily S
ES
Roughley
Peter J
PJ
Smith
Margaret M
MM
Kerr
Briedgeen
B
Hughes
Clare E
CE
Caterson
Bruce
B
Little
Christopher B
CB
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism; D058578:Biglycan; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism*; D058575:Decorin; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D000071235:Fibromodulin; D006621:Hip Joint / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007632:Keratan Sulfate / Q000378:metabolism*; D007719:Knee Joint / Q000378:metabolism / Q000473:pathology; D000071234:Lumican; D008297:Male; D008592:Menisci, Tibial / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D015207:Osteoarthritis, Hip / Q000378:metabolism* / Q000473:pathology; D020370:Osteoarthritis, Knee / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism*
C546884:BGN protein, human; D058578:Biglycan; D011508:Chondroitin Sulfate Proteoglycans; C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; C000604330:FMOD protein, human; C490948:KERA protein, human; C000604306:LUM protein, human; D000071234:Lumican; D010446:Peptide Fragments; D011509:Proteoglycans; D000071235:Fibromodulin; D007632:Keratan Sulfate