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Objective: This study aims to explore the relationship between PI3K/AKT/mTOR signaling pathway and autophagy of articular chondrocytes in rats with osteoarthritis (OA)., Methods: Rat articular chondrocytes were isolated and cultured, and then induced by protein inhibitors of PI3K/AKT/mTOR signaling pathway. Chondrocytes were assigned into blank group, IL-1β induction group (IL-1β group), PI3K inhibitor+IL-1β induction group (PI3Ki+IL-1β group), AKT inhibitor+IL-1β induction group (AKTi+IL-1β group) and mTOR inhibitor+IL-1β induction group (mTORi+IL-1β group). Cell proliferation activity was detected by MTT assay, cell cycle by flow cytometry and cell autophagy by monodansylcadaverine (MDC) staining. Autophagy rates were evaluated by GFP-LC3 fluorescence microscopy. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect mRNA expressions of autophagy-related genes (Atg5 and Atg7). Western blotting was utilized to detect expressions of autophagy markers (LC3, Beclin1 and p62) and of relevant proteins in the PI3K/AKT/mTOR signaling pathway., Results: The cell proliferation rate of the IL-1β group was lower than that of the blank group after cells were cultured for 24h, and the cell proliferation rates of the PI3Ki+IL-1β group, the AKTi+IL-1β group and the mTORi+IL-1β group were higher than those of the IL-1β group. In comparison with the blank group, cells in the IL-1β group were arrested at the G1 phase and decreased in the S phase, MDC positive staining cells were decreased with attenuated staining intensity, the autophagy rate was decreased, the mRNA expressions of Atg5 and Atg7 and the protein expressions of LC3, Beclin1 and p62 were significantly down-regulated. While in the groups of PI3Ki+IL-1β, AKTi+IL-1β and mTORi+IL-1β, haploid cells were reduced, coupled with an increased proportion of cells in the S phase and decreased proportion of cells in the G1 phase, the autophagy rate was increased, the mRNA expressions of Atg5 and Atg7 and the protein expressions of LC3, Beclin1 and p62 were significantly up-regulated. Compared with the blank group, the protein phosphorylation levels of PI3K, AKT and mTOR were elevated, while there were no significant difference observed in the total amount of PI3K, AKT and mTOR in the IL-1β group. Meanwhile, there were relatively low protein phosphorylation levels of PI3K, AKT and mTOR in the groups of PI3Ki+IL-1β, AKTi+IL-1β and mTORi+IL-1β., Conclusions: Inflammation could inhibit the proliferation and cell cycle of rat chondrocytes and reduce the autophagy rate. Inhibition of PI3K/AKT/mTOR signaling pathway could promote the autophagy of articular chondrocytes and attenuate inflammation response in rats with OA., (Copyright © 2017. Published by Elsevier Masson SAS.)

Hyaluronic acid (HA) plays multifaceted role in regulating various biological processes and maintaining homeostasis into the body. Numerous researches evidenced the biomedical implications of HA in skin repairmen, cancer prognosis, wound healing, tissue regeneration, anti-inflammatory, immunomodulation. The present review was aimed to summarize and critically appraise the recent developments and efficacy of HA for treatment of inflammatory skin and joint diseases. A thorough analysis of the literature revealed that HA based formulations ( i.e. , gels, creams, autologous graft, thin sheets, soaked gauze, gauze pad, tincture, injection) have shown remarkable efficacy in treating a wide range of inflammatory skin diseases. The safety, tolerability, and efficacy of HA (as intra-articular injection) have also been well-documented for treatment of various types of joint disease including knee osteoarthritic, joint osteoarthritis, canine osteoarthritis, and meniscal swelling. Intra-articular injection of HA produces remarkable reduction in joint pain, synovial inflammation, and articular swelling. A remarkable improvement in chondrocyte density, territorial matrix appearance, reconstitution of superficial amorphous layer of the cartilage, collagen remodelling, and regeneration of meniscus have also been evident in patients treated with HA. Conclusively, we validate that the application/administration of HA is a promising pharmacotherapeutic regimen for treatment of inflammatory skin and joint diseases. [ABSTRACT FROM AUTHOR]