Inhibition of interleukin-1β-stimulated matrix metalloproteinases via the controlled release of interleukin-1Ra from chitosan microspheres in chondrocytes.

The aim of the study was to determine whether the controlled release of interleukin (IL)-1Ra from chitosan (CS) microspheres inhibits the IL-1β-stimulated production of matrix metalloproteinases (MMPs) in chondrocytes. The CS-IL-1Ra microspheres were fabricated by an emulsification method using sodium tripolyphosphate as a crosslinker, and the controlled release of IL-1Ra was determined using an enzyme-linked immunosorbent assay. IL-1β was added to normal rat chondrocytes to stimulate MMP production. The chondrocytes were incubated with CS-IL-1Ra microspheres to assess its effects on IL-1β-induced MMP expression. Chondrocyte proliferation and glycosaminoglycan (GAG) content were also determined. The mRNA expression and protein levels of IL-1β, MMP-1, MMP-3 and MMP-13 were detected using reverse transcription-polymerase chain reaction and western blotting analyses, respectively. The IL-1Ra release kinetics were characterized by an initial burst release, which was reduced to a linear release over seven days. The mRNA expression levels and protein levels of IL-1β, MMP-1, MMP-3 and MMP-13 were reduced compared with the control group. The present study demonstrated the chondroprotective properties of CS microspheres as a controlled release system carrying IL-1Ra, due to the ability of the system to downregulate the expression of osteoarthritis-associated matrix-degrading proteinases in chondrocytes.