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. 2017 Apr 22;74(19):3451–3465. doi: 10.1007/s00018-017-2531-z

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]