Doxycycline inhibits collagen synthesis by bovine chondrocytes cultured in alginate

被引:25
作者
Beekman, B
Verzijl, N
deRoos, JADM
Koopman, JL
TeKoppele, JM
机构
[1] Gaubius Laboratory, Dept. of Vasc. and Connective T., TNO Prevention and Health, 2301 CE Leiden
关键词
D O I
10.1006/bbrc.1997.7088
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 mu M doxycycline, collagen synthesis was decreased by 50 %; no effect on cell proliferation (DNA levels) or general protein synthesis (S-35-Met and S-35-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. (C) 1997 Academic Press.
引用
收藏
页码:107 / 110
页数:4
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