An international joint research group led by YLC Project Assistant Professor Hiroki Iijima of Nagoya University revealed that osteoarthritis of the knee occurs when articular cartilage, which hardens with age, suppresses longevity proteins.Harvard University, University of Pittsburgh, Mayo Clinic, California Institute of Technology, and Kyoto University are participating in the research.
As articular cartilage ages, the components and structure of the extracellular matrix change.Remodeling of the extracellular matrix results in an increase in collagen fibers and cross-linking between collagen fibers, resulting in an age-dependent increase in tissue stiffness.Age-related changes in tissue physical properties are thought to cause tissue cell senescence and functional decline through abnormal mechanical signal transduction, but the underlying molecular mechanisms remain unclear.
Focusing on a longevity protein called α-Klotho, the research group has been analyzing the function of α-Klotho, whose expression decreases with age, in articular cartilage.As a result, it was found that cartilage tissue that hardens with age reduces the expression of α-Klotho and induces knee osteoarthritis.
Furthermore, this age-related decrease in α-Klotho expression is a result of increased recruitment of DNA methyltransferases and enhanced α-Klotho promoter methylation due to changes in the physical properties of the extracellular matrix surrounding cells. I also found out.These research results suggest that the physical properties of the extracellular matrix, its mechanical signaling, and α-Klotho may be novel therapeutic targets for cartilage therapy.
This time, the possibility of elucidating the pathology of osteoarthritis and developing a treatment method for osteoarthritis, for which there is no radical treatment, was shown.In addition, since the increase in tissue stiffness due to aging is not a feature specific to articular cartilage, it may contribute to elucidating the pathogenesis of age-related diseases in other organs.
Paper information:[Nature Communications] Age-related matrix stiffening epigenetically regulates α-Klotho expression and compromises chondrocyte integrity
