Doxycycline inhibits type XI collagenolytic activity of extracts from human osteoarthritic cartilage and of gelatinase.

Doxycycline was shown to inhibit digestion of exogenous type XI collagen by homogenates of human osteoarthritic cartilage in vitro. On SDS-PAGE, the cleavage products generated by cartilage extracts were larger and less abundant, indicating less complete cleavage, when doxycycline (10 or 30 microM) was added to the samples. The inhibitory effect was concentration dependent. Purified gelatinase from canine kidney epithelial cells, which also digests type XI collagen, was inhibited in a similar manner by doxycycline. If tetracyclines inhibit this metalloproteinase activity in articular cartilage in vivo, they could modify cartilage breakdown in osteoarthritis.