The amelioration of cartilage degeneration by photo-crosslinked GelHA hydrogel and crizotinib encapsulated chitosan microspheres

Oncotarget. 2017 May 2;8(18):30235-30251. doi: 10.18632/oncotarget.15750.

Abstract

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.

Keywords: angiogenesis; hydrogel; osteoarthritis.

MeSH terms

  • Animals
  • Biomarkers
  • Cartilage / drug effects*
  • Cartilage / metabolism
  • Cartilage / pathology*
  • Chitosan* / chemistry
  • Chondrocytes / drug effects
  • Chondrocytes / metabolism
  • Crizotinib
  • Disease Models, Animal
  • Drug Carriers
  • Drug Liberation
  • Gene Expression
  • Humans
  • Hydrogel, Polyethylene Glycol Dimethacrylate* / chemistry
  • Interleukin-1beta / metabolism
  • Interleukin-1beta / pharmacology
  • Mice
  • Microspheres*
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • Osteoarthritis / drug therapy
  • Osteoarthritis / genetics
  • Osteoarthritis / metabolism
  • Osteoarthritis / pathology
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein Kinase Inhibitors / chemistry
  • Pyrazoles / administration & dosage*
  • Pyrazoles / chemistry
  • Pyridines / administration & dosage*
  • Pyridines / chemistry
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Biomarkers
  • Drug Carriers
  • Interleukin-1beta
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyridines
  • Vascular Endothelial Growth Factor A
  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Crizotinib
  • Chitosan