Abstract
Osteoarthritis is mainly caused by a degenerative joint disorder, which is characterized by the gradual degradation of articular cartilage and synovial inflammation. The chondrocyte, the unique resident cell type of articular cartilage, is crucial for the development of osteoarthritis. Previous studies revealed that P21-activated kinase-1 (PAK1) was responsible for the initiation of inflammation. The purpose of the present study was to determine the potential role of PAK1 in osteoarthritis. The level of PAK1 expression was measured by Western blot and quantitative real-time PCR in articular cartilage from osteoarthritis model rats and patients with osteoarthritis. In addition, the functional role of aberrant PAK1 expression was detected in the chondrocytes. We found that the expression of PAK1 was significantly increased in chondrocytes treated with osteoarthritis-related factors. Increased expression of PAK1 was also observed in knee articular cartilage samples from patients with osteoarthritis and osteoarthritis model rats. PAK1 was found to inhibit chondrocytes proliferation and to promote the production of inflammatory cytokines in cartilages chondrocytes. Furthermore, we found that PAK1 modulated the production of extracellular matrix and cartilage degrading enzymes in chondrocytes. Results of the present studies demonstrated that PAK1 might play an important role in the pathogenesis of osteoarthritis.
Highlights
Osteoarthritis (OA) is one of the most prevalent age-related degenerative joint disorders, which cause pain and joint dysfunctions in the affected patients [1,2]
The results of Western blot showed that the protein expressions of pT423-P21-activated kinase-1 (PAK1) and PAK1 were significantly increased in rat chondrocytes treated with IL-1β (10 ng/ml) or tumor necrosis factor-α (TNF-α) (10 ng/ml) or 10% mechanical stress (Figure 1A–C)
The results showed that PAK1 was mainly distributed in cytoplasm and its fluorescence intensity was enhanced by 10 ng/ml IL-1β, 10 ng/ml TNF-α and 10% mechanical stress respectively (Figure 1E)
Summary
Osteoarthritis (OA) is one of the most prevalent age-related degenerative joint disorders, which cause pain and joint dysfunctions in the affected patients [1,2]. The gradual degradation of articular cartilage and synovial inflammation are thought to be the main pathological event responsible for the joint destruction and during development of OA [3]. Growing evidences suggested that mechanical, genetic factors and inflammatory processes within joint tissues were confirmed to associate with the onset and progression of OA [4]. Articular cartilage covers the surface of a diarthrodial joint, which is composed of only one cell type, chondrocytes, enclosed in a self-synthetized extracellular matrix (ECM). The chondrocyte plays a central role in the degradation of ECM, which maintains the balance between synthesis and degradation of the cartilage ECM [6,7]. Chondrocytes as quiescent cells cannot divide under physiological conditions [8]. Phenotypic stability, anabolic/catabolic homeostasis, and survival of chondrocytes are crucial for the maintenance of proper articular cartilage [9]
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