Host metalloproteinases in Lyme arthritis.
OBJECTIVE
To assess the role of matrix metalloproteinases (MMPs) in cartilage and bone erosions in Lyme arthritis


METHODS
We examined synovial fluid from 10 patients with Lyme arthritis for the presence of MMP-2, MMP-3, MMP-9, and "aggrecanase" activity using gelatinolytic zymography and immunoblot analysis. We developed an in vitro model of Lyme arthritis using cartilage explants and observed changes in cartilage degradation in the presence of Borrelia burgdorferi and/or various protease inhibitors.


RESULTS
Synovial fluid from patients with Lyme arthritis was found to contain at least 3 MMPs: gelatinase A (MMP-2), stromelysin (MMP-3), and gelatinase B (MMP-9). In addition, there was evidence in 2 patients of "aggrecanase" activity not accounted for by the above enzymes. Infection of cartilage explants with B. burgdorferi resulted in induction of MMP-3, MMP-9, and "aggrecanase" activity. Increased induction of these enzymes by B. burgdorferi alone was not sufficient to cause cartilage destruction in the explants as measured by glycosaminoglycan (GAG) and hydroxyproline release. However, addition of plasminogen, which can act as an MMP activator, to cultures resulted in significant GAG and hydroxyproline release in the presence of B. burgdorferi. The MMP inhibitor batimastat significantly reduced the GAG release and completely inhibited the collagen degradation.


CONCLUSIONS
MMPs are found in synovial fluids from patients with Lyme arthritis and are induced from cartilage tissue by the presence of B. burgdorferi. Inhibition of MMP activity prevents B. burgdorferi-induced cartilage degradation in vitro.
Hu
L T
LT
New England Medical Center, Boston, Massachusetts, USA.
Eskildsen
M A
MA
Masgala
C
C
Steere
A C
AC
Arner
E C
EC
Pratta
M A
MA
Grodzinsky
A J
AJ
Loening
A
A
Perides
G
G
D000818:Animals; D001170:Arthritis, Infectious / Q000201:enzymology* / Q000209:etiology; D015153:Blotting, Western; D015748:Borrelia burgdorferi Group / Q000235:genetics / Q000302:isolation & purification; D002356:Cartilage / Q000737:chemistry / Q000166:cytology; D002417:Cattle; D046508:Culture Techniques; D004269:DNA, Bacterial / Q000032:analysis; D010450:Endopeptidases / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006025:Glycosaminoglycans / Q000032:analysis; D006801:Humans; D007719:Knee Joint / Q000201:enzymology / Q000382:microbiology; D008193:Lyme Disease / Q000150:complications / Q000201:enzymology*; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D013582:Synovial Fluid / Q000201:enzymology / Q000382:microbiology
D004269:DNA, Bacterial; D006025:Glycosaminoglycans; D010450:Endopeptidases; D020782:Matrix Metalloproteinases; C083641:aggrecanase