crt-0066101 and Osteoarthritis

Inflammatory stress caused by protein kinase D (PKD) plays a critical role in damaging chondrocytes and extracellular matrix (ECM) during osteoarthritis (OA). The PKD inhibitor (PKDi) (CRT0066101) has been used to overcome inflammation in different cell types. However, the efficacy of a therapeutic drug can be limited due to off-target distribution, slow cellular internalization, and limited lysosomal escape. In order to overcome this issue, we developed nanosomes carrying CRT0066101 (PKDi-Nano) and tested their efficacy in vitro in chondrocytes.. Chondrocytes were subjected to IL-1β-induced inflammatory stress treated with either PKDi or PKDi-Nano. Effects of treatment were measured in terms of cytotoxicity, cellular morphology, viability, apoptosis, phosphorylation of protein kinase B (Akt), and anabolic/catabolic gene expression analyses related to cartilage tissue.. The effects of PKDi-Nano treatment were more pronounced as compared to PKDi treatment. Cytotoxicity and apoptosis were significantly reduced following PKDi-Nano treatment (. Taken together, these results suggest that PKDi-Nano can be used as a successful strategy to reduce IL1β-induced inflammatory stress in chondrocytes.

Topics: Animals; Apoptosis; Cells, Cultured; Chondrocytes; Gene Expression Regulation; Inflammation; Interleukin-1beta; Nanostructures; NF-kappa B; Osteoarthritis; Oxidative Stress; Phosphorylation; Protective Agents; Protein Kinase C; Proto-Oncogene Proteins c-akt; Pyrimidines; Swine