crizotinib and Osteoarthritis

The present study aimed to investigate the synergistic therapeutic effect of decreaseing cartilage angiogenesis via exposure to crizotinib encapsulated by chitosan microspheres and photo-crosslinked hydrogel, with the goal of evaluating crizotinib as a treatment for osteoarthritis. First, we developed and evaluated the characteristics of hydrogels and chitosan microspheres. Next, we measured the effect of crizotinib on the cartilage degeneration induced by interleukin-1β in chondrocytes. Crizotinib ameliorated the pathological changes induced by interleukin-1β via its anti-angiogenesis function. In addition, we surgically induced osteoarthritis in mice, which were then injected intra-articularly with crizotinib-loaded biomaterials. Cartilage matrix degradation, expression of vascular endothelial growth factor and extracellular signal-regulated kinases 1/2 were evaluated after surgery. Treatment with the combination of crizotinib-loaded biomaterials retarded the progression of surgically induced osteoarthritis. Crizotinib ameliorated cartilage matrix degradation by promoting anti-angiogenesis and impeding extracellular signal-regulated kinases 1/2 signaling pathway. Our results demonstrate that the combination of photo-crosslinked hydrogel and crizotinib-loaded chitosan microspheres might represent a promising strategy for osteoarthritis treatment.

Topics: Animals; Biomarkers; Cartilage; Chitosan; Chondrocytes; Crizotinib; Disease Models, Animal; Drug Carriers; Drug Liberation; Gene Expression; Humans; Hydrogel, Polyethylene Glycol Dimethacrylate; Interleukin-1beta; Mice; Microspheres; Neovascularization, Pathologic; Osteoarthritis; Protein Kinase Inhibitors; Pyrazoles; Pyridines; Vascular Endothelial Growth Factor A

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Crizotinib; Deoxycytidine; Gemcitabine; Humans; Lung Neoplasms; Male; Osteoarthritis; Protein Kinase Inhibitors; Pyrazoles; Pyridines