Table 2.

Validated targets for gene silencing strategies aimed at enhancing chondrogenesis—transcription factors

Target	Main function	Biological effect of gene silencing	References
RUNX2	Osteoblast differentiation	Chondrogenesis of hMSCs with reduced expression of collagen I and osteogenic markers in vitro and after injection in mice	[21, 42]
		Enhanced expression of SOX9 and increased synthesis of cartilage matrix (collagen II, aggrecan) in  chondrogenic progenitor cells. Reduced expression of collagen I and catabolic enzymes (MMP13, aggrecanase-2/ ADAMTS5)	[53]
		Enhanced expression of SOX9 and collagen II and loss of collagen I in chondrocytes derived from DDR-1 deficient mice (OA model)	[54]
TGIF1	Embryonic development	Enhanced chondrogenesis of rat tendon and bone marrow-derived MSCs in vitro. Improved fibrocartilage production and healing of bone-to-tendon insertion after in vivo implantation	[55–57]
SHOX2	Embryonic development	Chondrogenesis of mouse MSCs in the absence of chondro-stimulation without transition to the hypertrophic stage	[58]
TWIST1	EMT	Increased formation of chondrogenic nodules and expression of chondrogenic markers during micromass culture of murine limb bud mesenchymal cells	[59]
SLUG	EMT	Chondrogenesis of human bone marrow or Wharton’s jelly-derived hMSCs, and enhanced production of cartilage ECM onto HYAFF-11 scaffold	[60, 61]
p53	Cell cycle	Increased proliferation and expression of SOX9, collagen II, and aggrecan in progenitor cells isolated from human articular cartilage	[124]