Upon distraction it suggested that MSC number initially decline in the synovial fluid (SF) (figure 1A-B). MSCs present in the SF showed changes in their gene expression profile upon KJD, most clearly observed during the treatment (3 weeks; figure 1C).
GDF5 and Grem1 presented with a statistically significant increased expression (p<0.05) during treatment while FAB4 expression was decreased. ACAN, PTH1R, and DDR expression had the tendency to increase over time. ADAMTS4, SOX9 and PTHLH expression showed a trend to decrease over time.
Preliminary proteomics analysis on the SF samples of the first 5 patients indicate a clear difference can be seen in the samples before vs during and after distraction (see figure 2). Exact interpretation needs further analyses of the remaining patients. In parallel to this study we have analyzed (in collaboration with Oxford) the synovial fluid of joint distraction patients (additional group in addition to this project) for mechano-sensitive de/regenerative markers. Of the 10 markers studied 4 were significant elevated (IL-6, TGF-B, MCP-1, FGF-2), 2 significant downregulated (Activin-A, LTBP-2) and 4 were not changed (IL-8, MMP-3, TIMP-1, TSG-6). These results can give further guidance to the analyses performed in Paris.
This explorative study provides for the first-time data on changes in SF MSC number and their gene and protein expression profiles upon knee joint distraction. As such, first clues are provided for the involvement of MSCs in the regenerative process induced by joint distraction for end-stage knee OA. Final results are expected this summer. Further studies are necessary to unravel the processes involved