Human eIF5A adenoviral particles

Osteoarthritis (OA) is a chronic degenerative disease that causes chronic pain and long-term disability in middle-aged and elderly people. Eukaryotic translation initiation factor 5A (eIF5A) is a highly evolutionarily conserved translation factor that is required for maintaining cellular activity. The main function of eIF5A is to promote the elongation of messenger RNA (mRNA) encoding a specific peptide motif sequence. Here, researchers investigated how eIF5A regulates OA during mechanical overload and the specific mechanisms. Researchers created the destabilization of the medial meniscus (DMM) model and the mechanical overload-induced OA model and injected with overexpressing eIF5A adenovirus (eIF5A-ADV). After OA initiation, eIF5A led to upregulation of type II collagen (COL2) and downregulation of matrix metalloproteinase 13 (MMP13), P16, and P21, thereby delaying the progression of OA. Further sequencing and experimental results showed that eIF5A knockdown mediated activation of the Notch pathway by promoting the expression of the histone acetyltransferase cyclic AMP response element binding protein (CREB) binding protein (CREBBP), thereby accelerating the progression of OA. These findings identify a key functional mechanism for the onset of OA and suggest that intra-articular injection of eIF5A may be an effective therapeutic strategy for the treatment of OA.

Previous studies have shown that articular cartilage in the mouse knee joint undergoes proteoglycan loss and damage after being subjected to multiple loading fragments with a peak load of 13.5 N. Therefore, the researchers developed a model of excessive mechanical loading of 13.5 N. The eIF5A adenovirus was injected once a week for four weeks (Figure 1a). Pain was measured once a week, and the researchers found that mice also experienced knee pain after mechanical overload, which was partially relieved by adenovirus injection (Figure 1b). Notably, 13.5 N overload-induced OA mice also developed cartilage degeneration and joint tremors. The expression of eIF5A and COL2 was downregulated, while the expression of MMP13 and senescence markers P16 and P21 was upregulated (Figure 1c to 1n). Again, the eIF5A adenovirus could reverse this change. These results demonstrate the benign role of eIF5A in experimental OA.

Figure 1. Intra-articular injection of eukaryotic translation initiation factor 5A (eIF5A) partially relieved the progression of 13.5 N overload-induced osteoarthritis (OA). (Huang J, et al., 2025)