Protein-Degrading Enzymes In Osteoarthritis

ZEITSCHRIFT FUR ORTHOPADIE UND UNFALLCHIRURGIE(2021)

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摘要
Objective TGF beta 1 plays an important role in the metabolism of articular cartilage and bone; however, the pathological mechanism and targets of TGF beta 1 in cartilage degradation and uncoupling of subchondral bone remodeling remain unclear. Therefore, in this study, we investigated the relationship between TGF beta 1 and major protein-degrading enzymes, and evaluated the role of high levels of active TGF beta 1 in the thickening of subchondral bone and calcification of articular cartilage.Materials and Methods The expression of TGF beta 1 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 TGF beta 1, MMP-3, MMP-13 and IL-1 beta in cartilage and subchondral bone tissues were detected by absolute real-time quantitative RT-PCR. The expression of TGF beta 1, 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.Results Expression of TGF beta 1 and cartilage-degrading enzymes was higher in the cartilage-disrupted group than that in the intact group. Furthermore, expression of TGF beta 1, 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 platelike structure, the thickness of the trabecular bone is increased and the gap is small.Conclusions The data suggest that highly active TGF beta 1 activates the expression of cartilage-degrading enzymes. Abnormally activated TGF beta 1 may induce formation of the subchondral bone and expansion of the calcified cartilage area, eventually leading to degradation of the cartilage tissue.
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关键词
osteoarthritis (OA), transforming growth factor beta 1 (TGF beta 1), subchondral bone, bone remodeling
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