{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,6,6]],"date-time":"2024-06-06T21:19:18Z","timestamp":1717708758564},"reference-count":33,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2010,1,12]],"date-time":"2010-01-12T00:00:00Z","timestamp":1263254400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2010,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Tetracyclines were reported to slow down the progression of cartilage damage both in an animal model of osteoarthritis (OA) and in humans. In search for the underlying mechanisms we examined whether tetracyclines possess an inhibitory potential on the activity of aggrecanases and inflammatory mediators and can thus prevent proteoglycan (PG) loss from human articular cartilage. In vitro activity of aggrecanase\u20101 and \u20102 was recorded in the presence of 1\u2013100 \u00b5M tetracycline, minocycline, or doxycyline. Human knee articular cartilage explants were sorted according to the degree of OA and treated for 10 days with tetracycline derivatives in the presence of interleukin\u20101 (IL\u20101\u03b2). Synthesis and loss of PGs, nitric oxide (NO), and prostaglandin E<jats:sub>2<\/jats:sub> (PGE<jats:sub>2<\/jats:sub>), as well as the viability were determined. Tetracyclines derivatives dose\u2010dependently inhibited the activities of both aggrecanases in vitro, whereas no inhibitory effect of tetracyclines on any proteoglycanolytic activities within IL\u20101\u03b2\u2010treated human cartilage explants were found. Tetracyclines can significantly modulate NO and PGE<jats:sub>2<\/jats:sub> levels, but have no effect on PG synthesis and loss within the same human cartilage explant cultures. Altogether, our data show that tetracyclines have no inhibitory potential on any proteoglycanolytic activities within mild or moderately affected human OA cartilage at therapeutic achievable plasma levels. \u00a9 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. 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