As we get old, the chondrocytes in the joints will slowly age, and the cartilage mucus that acts as a lubricant will also decrease, causing joint pain, stiffness, and even osteoarthritis. Studies have shown that an important cause of osteoarthritis is the aging and functional deterioration of mesenchymal stem (precursor) cells, chondrocytes, and synoviocytes in the joints.
Researchers from the Institute of Biophysics of the Chinese Academy of Sciences examined and compared gene expression levels in young and old mesenchymal stem cells. They found that in the cell line of the elderly, one of the components of the PRC1 protein complex, CBX4 protein expression was lower, significantly lower than the young cell line. Later, they detected the primary mesenchymal stem cells isolated from the elderly tissue and found the same phenomenon.
Using the CRISPR/Cas9 technology to knockout of CBX4, the researchers found that mesenchymal stem cells lacking CBX4 did accelerate aging. The researchers cloned the CBX4 gene coding sequence into a lentiviral expression vector. When lentiviral vectors loaded with the CBX4 gene coding sequence were introduced into senescent human mesenchymal stem cells, these stem cells became more "young" and restored the characteristics of rapid growth. The researchers pointed out that this may be because CBX4 prevents the excessive synthesis of intracellular proteins, thereby slowing the rate of cellular aging.
In addition to cell-level experiments, the researchers conducted animal experiments. They cut the anterior cruciate ligament of the mouse to simulate the occurrence of osteoarthritis. The lentiviral vector overexpressing CBX4 was subsequently injected into the joint space of the mouse. It was found that the proportion of senescent cells in the joint was reduced, the cartilage regeneration was obvious, the inflammatory reaction was also suppressed, and the symptoms of osteoarthritis were effectively alleviated.
This study is the first to conceptually demonstrate the feasibility of gene-induced stem cell "younger" factor in the treatment of osteoarthritis, providing a new solution for the intervention of aging-related diseases, and has broad applications in geriatrics and regenerative medicine. prospect.
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