Protein-Degrading Enzymes in Osteoarthritis

TGFβ1 plays an important role in the metabolism of articular cartilage and bone; however, the pathological mechanism and targets of TGFβ1 in cartilage degradation and uncoupling of subchondral bone remodeling remain unclear. Therefore, in this study, we investigated the relationship between TGFβ1 and major protein-degrading enzymes, and evaluated the role of high levels of active TGFβ1 in the thickening of subchondral bone and calcification of articular cartilage.

The expression of TGFβ1 and protein-degrading enzymes in clinical samples of articular cartilage and subchondral bone obtained from the knee joint of patients with osteoarthritis was detected by immunohistochemistry. The expression levels of TGFβ1, MMP-3, MMP-13 and IL-1β in cartilage and subchondral bone tissues were detected by absolute real-time quantitative RT-PCR. The expression of TGFβ1, nestin and osterix in subchondral bone was detected by Western blot analysis and immunohistochemistry. The degree of subchondral bone thickening was determined by micro-computed tomography (CT) imaging.

Expression of TGFβ1 and cartilage-degrading enzymes was higher in the cartilage-disrupted group than that in the intact group. Furthermore, expression of TGFβ1, nestin and osterix was significantly higher in the OA group than that in the control group. Micro-CT imaging showed that in the OA group, the subchondral bone plate is thickened and the density is increased. The trabecular bone structure is thick plate-like structure, the thickness of the trabecular bone is increased and the gap is small.

The data suggest that highly active TGFβ1 activates the expression of cartilage-degrading enzymes. Abnormally activated TGFβ1 may induce formation of the subchondral bone and expansion of the calcified cartilage area, eventually leading to degradation of the cartilage tissue.