A boundary lubricant attaches and protects sliding bearing surfaces by preventing interlocking asperity-asperity contact. Proteoglycan-4 (PRG4) is a boundary lubricant found in the synovial fluid that provides chondroprotection to articular surfaces. Inflammation of the diarthrodial joint modulates local PRG4 concentration. Thus, we measured the effects of inflammation, with Interkeukin-1α (IL-1α) incubation, upon boundary lubrication and PRG4 expression in bovine cartilage explants. We further aimed to determine whether the addition of exogenous human recombinant PRG4 (rhPRG4) could mitigate the effects of inflammation on boundary lubrication and PRG4 expression in vitro.
Cartilage explants, following a 7-day incubation with IL-1α, were tested in a disc-on-disc configuration using either rhPRG4 or saline (PBS control) as a lubricant. Following mechanical testing, explants were studied immunohistochemically or underwent RNA extraction for RT-PCR. We found that static coefficient of friction (COF) significantly decreased to 0.14 ±0.065 from 0.21 ±0.059 (p=0.014) in IL-1α stimulated explants lubricated with rhPRG4, as compared to PBS. PRG4 expression was significantly up regulated from 30.8 ± 19 copies in control explants lubricated with PBS to 3330 ± 1760 copies in control explants lubricated with rhPRG4 (p<0.001). Explants stimulated with IL-1α displayed no increase in PRG4 expression upon lubrication with rhPRG4, but with PBS as the lubricant, IL-1α stimulation significantly increased PRG4 expression compared to the control condition from 30.8 ± 19 copies to 401 ± 340 copies (p=0.015). Overall, these data suggest that exogenous rhPRG4 may provide a therapeutic option for reducing friction in transient inflammatory conditions and increasing PRG4 expression.
Larson KM, Zhang L, Elsaid KA, Schmidt TA, Fleming BC, Badger GJ, Jay GD. Reduction of friction by recombinant human proteoglycan 4 in IL-1α stimulated bovine cartilage explants. J. Orthop. Res. 2016. doi:10.1002/jor.23367