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Doxycycline inhibits collagen synthesis by bovine chondrocytes cultured in alginate

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Author: Beekman, B. · Verzijl, N. · Roos, J.A.D.M.de · Koopman, J.L. · Tekoppele, J.M.
Type:article
Date:1997
Institution: Leiden, Netherlands Gaubius Instituut TNO
Source:Biochemical and Biophysical Research Communications, 1, 237, 107-110
Identifier: 234005
doi: doi:/10.1006/bbrc.1997.7088
Keywords: Biology · Biomedical Research · alginic acid · cysteine · methionine · collagen · glucuronic acid · hexuronic acid · messenger RNA · protein synthesis inhibitor · sulfur · articular cartilage · cell culture · cell proliferation · collagen synthesis · metabolic inhibition · nonhuman · osteoarthritis · phenotype · animal · biosynthesis · culture technique · cytology · dose response · drug effect · genetic transcription · metabolism · metacarpophalangeal joint · methodology · protein synthesis · Alginates · Animals · Cartilage, Articular · Cattle · Cell Culture Techniques · Cell Division · Cell Survival · Collagen · Cysteine · DNA · Dose-Response Relationship, Drug · Doxycycline · Glucuronic Acid · Hexuronic Acids · Kinetics · Metacarpophalangeal Joint · Methionine · Protein Biosynthesis · Protein Synthesis Inhibitors · RNA, Messenger · Sulfur Radioisotopes · Transcription, Genetic

Abstract

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 μM 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. Chemicals/CAS: alginic acid, 28961-37-7, 29894-36-8, 9005-32-7, 9005-38-3; cysteine, 4371-52-2, 52-89-1, 52-90-4; doxycycline, 10592-13-9, 17086-28-1, 564-25-0; methionine, 59-51-8, 63-68-3, 7005-18-7; sulfur 35, 15117-53-0; Alginates; alginic acid, 9005-32-7; Collagen, 9007-34-5; Cysteine, 52-90-4; DNA, 9007-49-2; Doxycycline, 564-25-0; Glucuronic Acid, 576-37-4; Hexuronic Acids; Methionine, 63-68-3; Protein Synthesis Inhibitors; RNA, Messenger; Sulfur Radioisotopes