ABSTRACT
OBJECTIVE: We aimed to explore the effect and mechanism of the Src inhibitor PP2 on osteoarthritis (OA) progression. METHODS: The protein expressions of Src, p-Src (y418) and p-FAK in normal and OA human chondrocytes were detected by immunofluorescence (IF) analysis. Chondrocytes from the femur and tibial plateau of 3-day-old mice were extracted and inoculated into 6-well plates. The chondrocytes were co-cultured with IL-1ß and different doses of PP2, and then the degeneration of extracellular matrix was analyzed. A mouse OA model was induced by destabilizing medial meniscectomy of the right knee. Two weeks after the operation, different doses of PP2 were injected intraperitoneally. The drug was given three times a week for 6 weeks, and then the mice were sacrificed. Histopathological, IF and immunoblotting analyses were used to detect key OA catabolic markers and protein expression and related signaling. RESULTS: The levels of Src, p-Src (y418) and p-FAK in the knee cartilage tissue of patients with OA were abnormally increased. After chondrocytes were co-treated with IL-1ß and different doses of PP2, the results showed that PP2 reduced the abnormal increase of ß-catenin, p-ß-catenin and other proteins induced by IL-1ß, and reversed the decrease of p-Smad3, aggrecan and collagen â ¡ protein levels. Meanwhile, intraperitoneal injection of PP2 in vivo significantly reduced the degeneration of articular cartilage in the OA mouse model. CONCLUSION: Our data indicate that targeting Src with PP2 protected against cartilage destruction in an OA mouse model by inhibiting Wnt/ß-catenin and activating TGF-ß/Smad signaling, suggesting that Src may be a potential therapeutic target for OA treatment.
Subject(s)
Cartilage, Articular , Osteoarthritis , Humans , Mice , Animals , beta Catenin/metabolism , Wnt Signaling Pathway , Osteoarthritis/metabolism , Chondrocytes , Cartilage, Articular/pathology , Disease Models, Animal , Transforming Growth Factor beta/metabolism , Cells, CulturedABSTRACT
Developing low-cost and high-efficiency electrocatalysts to electrolyze water is an effective method for large-scale hydrogen production. For large-scale commercial applications, it is crucial to call for more efficient electrocatalysts with high-current density (≥1000 mA cm-2). However, it is challenging to simultaneously promote the large-scale production and hydrogen evolution reaction (HER) activity of these hydrogen catalysts. Herein, we report the large area tungstic disulfide-carbide (W/WS2-WC) heterojunction electrode vertically grown on an industrial-grade tungsten substrate by the solid-state synthesis method. The W/WS2-WC heterojunction electrode achieves a low overpotential of 473 mV at 1000 mA cm-2 in alkaline electrolytes.
ABSTRACT
Herein, we demonstrate a chemical vapor deposition route to the controlled growth of large scale MoS2/MoSe2 vertical van der Waals heterostructures on a molten glass substrate using water as the oxidizing chemical to guarantee a sufficient and uniform delivery of the metal precursor. This work offers an efficient way for developing other layered heterostructures for integrated electronic and optoelectronic devices.