Table 4.

Validated targets for gene silencing strategies aimed at enhancing chondrogenesis—matrix and secreted proteins

Target	Main function	Biological effect of gene silencing	References
Collagen I	ECM structural component	Enhanced chondrogenic potential of human dedifferentiated chondrocytes cultured in collagen sponges. Enhanced production of collagen II and aggrecan after subcutaneous implantation in mice	[36]
		Increased synthesis of collagen II, aggrecan, COMP and GAGs in pig synovial MSCs	[77]
HTRA1	Regulation of the availability of IGFs	Enhanced chondrogenic potential of human dedifferentiated chondrocytes cultured in collagen sponges. Enhanced production of collagen II and aggrecan after subcutaneous implantation in mice	[36]
Decorin	ECM structural component	Increased expression of SOX9, biglycan, and aggrecan in hMSCs	[78]
Lumican	ECM structural component	Augmented production of collagen II and increased fibril diameter in bovine chondrocytes	[79]
Asporin	ECM structural component	Increased expression of collagen II, aggrecan, and TGF-β1 in human chondrocytes	[80]
Aggrecanase-1/2	Catabolism of cartilage ECM	Enhanced proliferation, abundance of GAGs and total collagen, and expression of collagen II and aggrecan in rat chondrocytes cultured on a chitosan–gelatin scaffold	[81]
MMP2	Catabolism of cartilage ECM	Increased expression of fibronectin, integrin α5 and β1 in chicken limb bud mesenchymal cells. Enhanced precartilage condensation and GAGs production	[82]
VEGF	Vasculogenesis and angiogenesis	Enhanced production of collagen II, aggrecan and chondromodulin 1 during pellet culture of chondrocytes. Suppression of RUNX2, MMP13 and ALP. Protection from pro-hypertrophic stimuli (TNFα)	[83]
AIMP1	Angiogenesis and inflammation	Enhanced production of collagen II, aggrecan and GAGs in dedifferentiated and OA chondrocytes in vitro. Enhanced cartilage tissue formation in vivo	[23]
ANGPTL4	Lipid metabolism	Increased expression of collagen II and aggrecan, and suppression of MMP1, 3 and 13 in hMSCs	[37]