Title
Doxycycline inhibits collagen synthesis by differentiated articular chondrocytes.
Author
TeKoppele, J.M.
Beekman, B.
Verzijl, N.
Koopman, J.L.
de Groot, J.
Bank, R.A.
Gaubius Instituut TNO
Publication year
1998
Abstract
Doxycycline (DOX) profoundly inhibited collagen synthesis by differentiated articular chondrocytes. At 25 microM, the rate of collagen synthesis was suppressed by more than 50% without affecting cell proliferation (DNA levels) and general protein synthesis (35S-Met and 35S-Cys incorporation). Steady-state mRNA levels of type II collagen were also reduced, indicating that DOX may have an effect at the transcriptional level of type II collagen. The IC50 value of DOX to downregulate collagen synthesis (17 microM) is close to DOX levels attained in vivo (< 10 microM), and it is more than ten-fold lower than the IC50 values to inhibit the activity of most matrix metalloproteinases (MMPs). As such, these findings support the hypothesis that the reduced severity of OA observed in the dog anterior cruciate ligament model resulting from prophylactic treatment with DOX may involve mechanisms other than MMP inhibition alone. Our findings suggest that prevention of changes in the chondrocyte phenotype may be involved in the beneficial effect of doxycycline in experimental osteoarthritis, for differentiated chondrocytes in early stages of osteoarthritis exhibit elevated collagen synthesis.
Subject
Biology
Biomedical Research
antiinfective agent
collagen
doxycycline
metalloproteinase
protein synthesis inhibitor
proteinase inhibitor
animal
article
articular cartilage
biosynthesis
cartilage cell
cattle
cell culture
cytology
dog
drug antagonism
metabolism
osteoarthritis
Animals
Anti-Bacterial Agents
Cartilage, Articular
Cattle
Cells, Cultured
Chondrocytes
Collagen
Dogs
Doxycycline
Metalloendopeptidases
Osteoarthritis
Protease Inhibitors
Protein Synthesis Inhibitors
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TNO identifier
234662
ISSN
0895-9374
Source
Advances in dental research, 12 (2), 63-67
Document type
article