The role of alpha-1-protease inhibitor (A1PI) in the inhibition of protease activity in human knee osteoarthritis.
Alpha-1-protease inhibitor (A1PI) is the most abundant serum protease inhibitor, exhibiting inhibition of proteases known to act in osteoarthritis (OA) and rheumatoid arthritis. We have previously purified and sequenced A1PI synthesized by human articular cartilage and demonstrated in vitro protection from IL-1-induced proteoglycan (PG) degradation at a concentration of 1 mg/ml. In this study, the chondroprotective role of A1PI and possible inhibition of protease activity in OA, IL-1 and LPS-induced and aged normal human knee articular cartilage was investigated by immunohistochemical and in vitro methods. A variable low response to PG-degradation induction and to added A1PI protection of aged normal and OA cartilages was noted, while there was decreased constituative A1PI noted in OA cartilages as compared to normal.
Awbrey
B J
BJ
Orthopaedic Research Laboratories, Massachusetts General Hospital, Boston.
Kuong
S J
SJ
MacNeil
K L
KL
Wright
M
M
D000368:Aged; D002358:Cartilage, Articular / Q000201:enzymology* / Q000473:pathology; D004591:Electrophoresis, Polyacrylamide Gel; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000494:pharmacology; D007719:Knee Joint / Q000378:metabolism / Q000473:pathology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008666:Metalloendopeptidases / Q000378:metabolism; D010003:Osteoarthritis / Q000201:enzymology* / Q000473:pathology; D010447:Peptide Hydrolases / Q000378:metabolism; D000515:alpha 1-Antitrypsin / Q000502:physiology*
D007375:Interleukin-1; D008070:Lipopolysaccharides; D000515:alpha 1-Antitrypsin; D010450:Endopeptidases; D010447:Peptide Hydrolases; C022474:proteoglycan-degrading metalloendopeptidases; D008666:Metalloendopeptidases; C030895:caseinase