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] |