Up-regulation of P21-activated kinase 1 in osteoarthritis chondrocytes is responsible for osteoarthritic cartilage destruction

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.

Sterically stabilized liposomes targeting P21 (RAC1) activated kinase‑1 and secreted phospholipase A₂ suppress prostate cancer growth and metastasis

“…This was observed in two different models of PCa metastasis, representing two different strains of mice, which supports the rigor of our findings. Since PAK1 hyperactivation has also been reported in other diseases, such as osteoarthritis ( 57 ), neurodevelopmental disorders ( 58 ), macrocephaly ( 59 ), intellectual disability ( 60 ), and kidney injury ( 61 ), liposomal IPA3 could have potential therapeutic applications for several non-cancer human diseases.…”

miR-155 inhibits chondrocyte pyroptosis in knee osteoarthritis by targeting SMAD2 and inhibiting the NLRP3/Caspase-1 pathway

“…Osteoarthritis (OA) is a prevalent form of the degenerative joint disorder characterized by synovial inflammation and the gradual degradation of the articular cartilage, and the knee is the major peripheral joint affected causing progressive loss of the function, stiffness and pain [ 1 , 2 ]. Various personal level of risk factors for OA are identified, including genetic predispositions, sociodemographic characteristics such as female sex, diet-related factors, high bone density/mass, and obesity [ 3 ].…”