Table 3.

Validated targets for gene silencing strategies aimed at enhancing chondrogenesis—intracellular co-regulators and enzymes

Target	Main function	Biological effect of gene silencing	References
YAP	Proliferation and apoptosis	Increased expression of SOX9, collagen II and aggrecan, and decreased collagen I in rat articular chondrocytes	[63]
p16	Cell cycle	Enhanced proliferation of OA chondrocytes and recovered expression of collagen II and aggrecan without increase of collagen I. Enhanced response to TGF-β1 and protection from inflammatory stimuli (IL-1α)	[64]
p21	Cell cycle	Enhanced proliferation during expansion and collagen II and GAGs production during pellet culture of murine iPS. Maintenance of the chondrogenic potential of extensively passaged cells. Suppression of collagen I and X	[22]
GADD45β	Cell cycle	Suppressed terminal differentiation and expression of MMP13 in murine rib growth plate chondrocytes	[65]
ERK5, MEK5	Proliferation and differentiation	Enhanced expression of SOX5, SOX6, SOX9, collagen II, aggrecan, and GAGs production in hMSCs. Enhancement of the chondrogenic potential even in the absence of TGF-β	[66]
IKKα/β	Inflammation	Increased cartilage ECM production (collagen II, GAGs) and suppression of terminal differentiation in OA chondrocytes. Inhibition of the IL-1β mediated increase of MMP13	[67]
p53R2	DNA repair	Increased production of collagen II, aggrecan and GAGs in OA chondrocytes after tensile strain.	[68]
PHD2	Response to hypoxia	Upregulation of SOX9 and increased production of the cartilage ECM components collagen II, IX, XI, and aggrecan under normoxic or hypoxic conditions	[69]
KDM2A	Chromatin remodeling	Enhanced chondrogenesis of apical papilla-derived hMSCs	[70]
Raptor	Proliferation	Enhanced chondrogenesis of amniotic fluid-derived hMSCs with increased AKT activation, upregulation of HIF-2α and increased SOX9 and collagen II abundance	[120]