Abstract
15-Lipoxygenase-1 (15-LO-1) is involved in many pathological processes. The purpose of this study was to determine the potential role of 15-LO-1 in osteoarthritis (OA). The levels of 15-LO-1 expression were measured by western blotting and quantitative real-time PCR in articular cartilage from the OA rat models and OA patients. To further investigate the effects of 15-LO-1 on chondrocyte functions, such as extracellular matrix (ECM) secretion, the release of matrix-degrading enzymes, the production of reactive oxygen species (ROS), cell proliferation and apoptosis, we decreased or increased 15-LO-1 expression in chondrocytes by means of transfecting with siRNA targeting 15-LO-1 and plasmid encoding 15-LO-1, respectively. The results showed that 15-LO-1 expression was obviously increased in articular cartilage from OA rats and OA patients. It was also found that many factor-related OA, such as mechanical loading, ROS, SNP and inflammatory factor, significantly promoted 15-LO-1 expression and activity in chondrocytes. Silencing 15-LO-1 was able to markedly alleviate mechanical loading-induced cartilage ECM secretion, cartilage-degrading enzyme secretion and ROS production. Overexpression of 15-LO-1 could inhibit chondrocyte proliferation and induce chondrocyte apoptosis. In addition, reduction of 15-LO-1 in vivo significantly alleviated OA. Taken together, these results indicate that 15-LO-1 has an important role in the disease progression of OA. Thus 15-LO-1 may be a good target for developing drugs in the treatment of OA.
Highlights
Osteoarthritis (OA), the most common chronic joint disease, affects millions of patients worldwide
Quantitative real-time PCR analysis showed that the mRNA expression of COL2α1 and aggrecan were significantly decreased in OA patients compared with normal persons, whereas matrix metalloproteinase (MMP)-1 and MMP-13 mRNA expression were upregulated in OA patients, suggesting that OA patients’ samples were reliable (Figure 1a)
We found that the expression of 15-LO-1 was obviously upregulated in knee articular cartilage from OA patients, whereas more obvious increasing was observed in weight-bearing area compared with non-weight-bearing area (Figures 1b and c)
Summary
Osteoarthritis (OA), the most common chronic joint disease, affects millions of patients worldwide. As the sole cell type in cartilage, is the sensor of articular cartilage homeostasis and has a critical role in maintaining the normal physiological structure and function of articular cartilage.[4] Chondrocytes are responsible for the synthesis, maintenance and degradation of the cartilage extracellular matrix (ECM), which protects the tissue against tensile stress and physical loading.[5,6,7] Previous studies demonstrated that articular chondrocyte homeostasis could be disrupted by multiple factors, such as abnormal mechanical loading, pro-inflammatory mediators and oxidative stress.[1,3,8] identification of the changes in chondrocytes is critical for understanding the pathogenesis of OA and may lead to the development of new therapeutic targets for the treatment of the disease. These data suggest that 15-LO-1 may be a crucial factor for the pathogenesis of OA
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