Table 4.
Transcription factors.
| References | Objectives | Study design | Disease models | Delivery methods | Targets | Effects |
|---|---|---|---|---|---|---|
| Cucchiarini et al. (66) | Evaluate the combinatorial effect of FGF-2 and Sox9 via rAAV gene transfer upon the OA cartilage | Preclinical in vitro and in situ | Human articular OA chondrocytes (3D culture model) and OA cartilage explants | Adenoassociated virus: rAAV-hFGF-2; rAAV-FLAG-hsox9 | FGF-2 SOX9 | Improvement both survival and proliferation of chondrocytes with single overexpression of FGF-2; Combination of FGF-2 and Sox-9 ↑production of proteoglycans and type-II collagen, ↓ expression of type-X collagen |
| Daniels et al. (67) | Evaluate the effects of rAAV-mediated sox9 overexpression on the biological activities of human OA chondrocytes | Preclinical in vitro | Human articular OA chondrocytes (3D culture model) | Adenoassociated virus: rAAV-FLAG-hsox9 | SOX9 | Significant production of major matrix components (proteoglycans and type-II collagen) |
| Tao et al. (68) | Assess the effect of TGF-beta and SOX9 co-overexpression | Preclinical in vitro and in situ | Human OA chondrocyte monolayer cultures and alginate spheres; human OA explant cultures | Adenoassociated virus: rAAV-hTGF-beta; rAAV-FLAG-hsox9 | TGF-beta SOX9 | Increased proliferation and cell density; enhanced deposition of matrix proteoglycans; enhanced type-II collagen deposition; enhanced levels of chondrogenic SOX9, ACAN and COL2A1 expression; reduced type-X-collagen expression |
| Urich et al. (69) | Investigate the ability of polymeric micelles to deliver therapeutic rAAV-FLAG-hsox9 into human OA chondrocytes | Preclinical in vitro | Human primary OA chondrocytes in presence of pro-inflammatory cytokines | Adenoassociated virus: rAAV-FLAG-hsox9/Polymerci micelles | SOX9 | Increased type-II collagen deposition; increased proliferation and proteoglycan deposition |
| Kawata et al. (70) | Evaluate the therapeutic effects of KLF4 and KLF2 for OA | Preclinical in vitro | Human OA chondrocytes, meniscal cells and BMSCs | Adenovirus: Ad-KLF2 and Ad-KLF4 | KLF2 and KLF4 | Upregulation of cartilage genes |
| Preclinical in vivo | Mouse DMM model | Adenoassociated virus: AAV-KLF4 | KLF4 | Upregulation of cartilage genes; improved pain; improved OARSI score, meniscus histopathological score, synovitis score and bone score | ||
| Wang et al. (71) | Explore therapeutic effects of serum-derived exosomes from OA mice | Preclinical in vivo | Mouse anterior medial meniscus excision OA model | OA exosomes: ATF4-OA-Exo | ATF4 | Alleviated cartilage damage of OA mice (proteoglycan loss, increased Mankin score and increased osteophytes); increased COL-II and decreased MMP13 and inflammatory cytokines; partial recovery of weakened autophagy; inhibited TM/TNF-alpha induced chondrocyte apoptosis |