Proteoglycan-degrading activity of human stromelysin-1 and leukocyte elastase in rabbit joints. Quantitation of proteoglycan and a stromelysin-induced HABR fragment of aggrecan in synovial fluid and cartilage.
The objective of this study was to compare the specificity and potency of recombinant human SLN-1 (rhSLN) and human leukocyte elastase (HLE) as proteoglycan (PG)-degrading enzymes after intraarticular injection into rabbits. Another objective was to evaluate the elicitation of a rhSLN-induced hyaluronan-binding region (HABR) fragment from rabbit aggrecan in joints using a polyclonal antiserum (anti-FVDIPEN) against the synthetic peptide, Phe-Val-Asp-Ile-Pro-Glu-Asn (FVDIPEN). The intraarticular injection of either activated rhSLN or HLE resulted in enzyme-specific quantitative release of PG fragments into synovial fluid. Based on the criteria used herein, HLE appears to be a more potent PG-degrading enzyme than SLN. Intraarticular injection of rhSLN also resulted in time- and dose-dependent release of a new HABR fragment of aggrecan (HABR-FMDIPEN) into both articular cartilage and synovial fluid. HABR-FVDIPEN is likely to be a good marker of matrix metalloproteinase (MMP)-induced degradation of aggrecan.
Olszewski
J M
JM
Department of Pharmacology, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
Moore
V L
VL
McDonnell
J
J
Williams
H
H
Saphos
C A
CA
Green
B G
BG
Knight
W B
WB
Chapman
K T
KT
Hagmann
W K
WK
Dorn
C P
CP
Hale
J J
JJ
Mumford
R A
RA
D053674:Aggrecans; D000595:Amino Acid Sequence; D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016326:Extracellular Matrix Proteins; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism; D007596:Joints / Q000378:metabolism*; D037181:Lectins, C-Type; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D008969:Molecular Sequence Data; D011509:Proteoglycans / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D013582:Synovial Fluid / Q000378:metabolism*; D013997:Time Factors
D053674:Aggrecans; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D061965:Matrix Metalloproteinase Inhibitors; D011509:Proteoglycans; D006820:Hyaluronic Acid; D019272:Leukocyte Elastase; D019278:Matrix Metalloproteinase 3