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Synoviocytes are more sensitive than cartilage to the effects of minocycline and doxycycline on IL‐1α and MMP‐13‐induced catabolic gene responses
Author(s) -
Fortier Lisa A.,
Motta Tatiana,
Greenwald Robert A.,
Divers Thomas J.,
Mayr Karen G.
Publication year - 2010
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.21006
Subject(s) - minocycline , doxycycline , aggrecan , matrix metalloproteinase , cartilage , adamts , chondrocyte , matrix metalloproteinase 3 , chemistry , pharmacology , microbiology and biotechnology , medicine , metalloproteinase , pathology , osteoarthritis , biochemistry , biology , antibiotics , anatomy , thrombospondin , articular cartilage , alternative medicine
The objective of this study was to determine the primary articular tissue target of doxycycline and minocycline. Synoviocytes—cartilage cocultures ( n = 4) were treated with MMP‐13 (25 ng/mL medium) or IL‐1 (1.0 ng/mL medium) for 24 h. Doxycycline (4.3, 0.43, 0.043 µM) or minocycline (10, 1.0 or 0.1 µM) were then added and cultures were continued for 96 h. Cartilage and media were analyzed for GAG content. Quantitative PCR was used to measure cartilage MMP‐3, MMP‐13, aggrecan, COL2A1, ADAMTS‐4, and ADAMTS‐5 expression, and synoviocyte MMP‐3, MMP‐13, ADAMTS‐4, and ADMATS‐5 expression. Total and active MMP‐3, MMP‐13, and ADAMTS 4/5 enzymes were measured in culture medium. All concentrations of doxycycline and minocycline diminished GAG accumulation in the media. All concentrations of minocycline, but only the highest concentration of doxycycline decreased MMP‐3 and MMP‐13 expression in synoviocytes but not cartilage, and basal ADAMTS‐5 mRNA levels in both synoviocytes and cartilage. Only minocycline decreased active MMP‐13 protein in synoviocytes. In summary, the protective effects of tetracycline compounds are more pronounced in synoviocytes than cartilage, and following minocycline compared to doxycycline. Studies to determine the molecular mechanism of action of the tetracyclines in synoviocytes might lead to the design of targeted therapeutics for the treatment of OA or RA. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:522–528, 2010