Proteoglycan structural changes in human rheumatoid articular cartilage.
Human rheumatoid arthritic (RA) cartilage contains elevated levels of proteolytic enzymes in which the metalloproteases are believed to be the prime enzyme system involved in cartilage metabolism. We examined the effects of these enzymes and the serine proteases on endogenous proteoglycans (PGs) and newly synthesized PGs of seven RA cartilages. The data was further analyzed with regard to the therapy received by the patients prior to surgery. A structural heterogeneity among the PGs from RA cartilage was found, and two subsets were distinguished. While in the first subset more than 35% of the PGs were in aggregate form, no appreciable amount of PG aggregate was found in the second subset. Interestingly, in all but one specimen the subsets appeared to be a function of prior therapy received by the patients. In subset I patients had received prednisone and/or DMARD in addition to NSAIDs, while those from subset II had all received NSAIDs only, with one exception. Our findings also suggest that PG structure alterations could result from the action of already active and APMA-activated metalloproteases; these reduced the PG aggregation capability and caused extensive cleavage in the PG core protein. The serine proteases did not seem to play a major role. Moreover, when the endogenous latent metalloproteases were activated with APMA, high-density PGs (the A1D1 fraction) showed a reduction in their capacity to reaggregate, and in their hydrodynamic size. Using an immunological technique we demonstrated the presence, in subset I, of the hyaluronan binding region domain (HABR) of the core protein. For subset II this domain could not be found.(ABSTRACT TRUNCATED AT 250 WORDS)
Martel-Pelletier
J
J
Unité des Maladies Rhumatismales, Hôpital Notre-Dame, Université de Montréal, Canada.
Pelletier
J P
JP
Cloutier
J M
JM
Rebert
N
N
Malemud
C J
CJ
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D015153:Blotting, Western; D002358:Cartilage, Articular / Q000737:chemistry* / Q000201:enzymology / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism; D008297:Male; D008666:Metalloendopeptidases / Q000032:analysis / Q000502:physiology; D008875:Middle Aged; D011241:Prednisone / Q000494:pharmacology; D011509:Proteoglycans / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D012697:Serine Endopeptidases / Q000032:analysis / Q000502:physiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011509:Proteoglycans; D006820:Hyaluronic Acid; D012697:Serine Endopeptidases; D008666:Metalloendopeptidases; D011241:Prednisone