Liposomic lubricants suppress shear-stress induced inflammatory gene regulation in the joint in vivo

Abstract

Osteoarthritis (OA) is a widespread, debilitating joint disease associated with articular cartilage degradation. It is driven via mechano-inflammatory catabolic pathways, presumed up-regulated due to increased shear stress on the cartilage-embedded chondrocytes, that lead to tissue degeneration. Here we demonstrate that the up-regulation of the matrix metalloproteinase 3 (Mmp3) and interleukin-1beta (Il1b) genes upon surgical joint destabilization in a model of murine OA is completely suppressed when lipid-based lubricants are injected into the joints. At the same time, Timp1, a compression but not shear-stress sensitive gene, is unaffected by lubricant. Our results provide direct evidence that biolubrication couples to catabolic gene regulation in OA, shed strong light on the nature of the chondrocytes' response to shear stress, and have clear implications for novel OA treatments.