Doxyclycline inhibits collagen synthesis by bovine chondrocytes cultured in alginate.
Doxycycline is known for its ability to inhibit matrix metalloproteinases (MMPs), a family of enzymes that play a role in cartilage breakdown in arthritides. Its prophylactic effect in reducing joint degradation in osteoarthritis is mainly attributed to this property. In this study, we show that doxycycline exhibits a profound inhibition of collagen synthesis by bovine articular chondrocytes cultured in alginate. At 25 microM doxycycline, collagen synthesis was decreased by 50%; no effect on cell proliferation (DNA levels) or general protein synthesis (35S-Met and 35S-Cys incorporation) was observed. Messenger RNA levels of type II collagen were also reduced, indicating an effect of doxycycline at the transcriptional level. The concentration of doxycycline needed to downregulate collagen synthesis was > 10-fold lower than that needed to inhibit most of the MMPs. Inasmuch as differentiated chondrocytes in the early stages of osteoarthritis exhibit increased collagen synthesis, the beneficial effect of doxycycline in vivo may involve prevention of changes in chondrocyte phenotype.
Beekman
B
B
Gaubius Laboratory, Department of Vascular and Connective Tissue Research, TNO Prevention and Health, Leiden, The Netherlands.
Verzijl
N
N
de Roos
J A
JA
Koopman
J L
JL
TeKoppele
J M
JM
D000464:Alginates; D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002417:Cattle; D018929:Cell Culture Techniques / Q000379:methods; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival; D003094:Collagen / Q000096:biosynthesis*; D003545:Cysteine / Q000378:metabolism; D004247:DNA / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004318:Doxycycline / Q000494:pharmacology*; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D007700:Kinetics; D008662:Metacarpophalangeal Joint; D008715:Methionine / Q000378:metabolism; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger / Q000096:biosynthesis; D013462:Sulfur Radioisotopes; D014158:Transcription, Genetic / Q000187:drug effects*
D000464:Alginates; D006603:Hexuronic Acids; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D013462:Sulfur Radioisotopes; D020723:Glucuronic Acid; D003094:Collagen; D004247:DNA; D008715:Methionine; D003545:Cysteine; D004318:Doxycycline