title: 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.
abstract: 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.
authors.affiliation: Department of Pharmacology, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Olszewski
authors.forename: V L
authors.initials: VL
authors.lastname: Moore
authors.forename: J
authors.initials: J
authors.lastname: McDonnell
authors.forename: H
authors.initials: H
authors.lastname: Williams
authors.forename: C A
authors.initials: CA
authors.lastname: Saphos
authors.forename: B G
authors.initials: BG
authors.lastname: Green
authors.forename: W B
authors.initials: WB
authors.lastname: Knight
authors.forename: K T
authors.initials: KT
authors.lastname: Chapman
authors.forename: W K
authors.initials: WK
authors.lastname: Hagmann
authors.forename: C P
authors.initials: CP
authors.lastname: Dorn
authors.forename: J J
authors.initials: JJ
authors.lastname: Hale
authors.forename: R A
authors.initials: RA
authors.lastname: Mumford
mesh_terms: 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
chemical_list: 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