Combination Gene Therapy for α-Klotho and TGFβR2 Improves Osteoarthritis in Mice

Researchers here report that upregulation of α-Klotho and TGFβR2 together, via gene therapy, can modestly reverse osteoarthritis in a rat model in which untreated animals progress to a more severe stage of the condition. Inhibiting TGF-β receptors such as TGFβR2 is known to suppress chronic inflammation, and likely functions by interfering in the inflammatory TGF-β signaling produced by senescent cells. The evidence for cellular senescence to drive the progression of osteoarthritis is quite compelling at this point. Meanwhile, α-Klotho declines with age and upregulation of this protein is known to improve regenerative capacity in some tissues. Osteoarthritis is caused by gradual changes to cartilage that cushions bones and joints. During aging and repetitive stress, molecules and genes in the cells of this articular cartilage change, eventually leading to the breakdown of the cartilage and the overgrowth of underlying bone, causing chronic pain and stiffness. Previous research had pinpointed two molecules, αKLOTHO and TGF beta receptor 2 (TGFβR2), as potential drugs to treat osteoarthritis. αKLOTHO acts on the mesh of molecules surrounding articular cartilage cells, keeping this extracellular matrix from degrading. TGFβR2 acts more directly on cartilage cells, stimulating their proliferation and preventing their breakdown. Researchers treated young, otherwise healthy rats with osteoarthritis with viral particles containing the DNA instructions for ma...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs