Manipulating co-regulators of RUNX and SOX9 to enhance the chondrogenic potential of chondrogenic progenitor cells in osteoarthritis

The regeneration of diseased hyaline cartilage continues to be a great challenge, mainly because degeneration overtaxes the tissue’s self-renewal capacity. Recently, we demonstrated that repair tissue from human articular cartilage during the late stages of osteoarthritis harbors a unique progenitor cell population, termed chondrogenic progenitor cells (CPCs). Down-regulation of the osteogenic transcription factor RUNX2 enhanced the expression of the chondrogenic transcription factor SOX9. This, in turn, increased the matrix synthesis potential of the CPCs without altering their migratory capacity (Koelling et al., 2009, Cell Stem Cell). We now present unpublished data on the role of co-regulators of SOX9 and RUNX2 to enhance the chondrogenic potential of CPCs. Candidate molecules for example, RAB5C, YWHAE or DDX5, identified in an elaborated knock-down and pull down experiment have been overexpressed or knocked-out via CRISPR/Cas9 to elucidate their influence on the chondrogenic behavior of CPCs. The results indicate, that the chondrogenic potential of CPCs can be enhanced via the manipulation of co-regulators of SOX9 and RUNX2.