In a recent study at Salk Institute, researchers found that a powerful combination of two experimental drugs could reverse the cellular and molecular signs of osteoarthritis in rats as well as in human cartilage cells.
They say that this is potentially a therapy that can be translated to the clinic quite easily.
The study is published in the journal Protein & Cell. One author is Juan Carlos Izpisua Belmonte, a professor in Salk’s Gene Expression Laboratory.
Affecting 30 million adults, osteoarthritis is the most common joint disorder in the United States and its prevalence is expected to rise in the coming years due to the aging population and increasing rate of obesity.
The disease is caused by gradual changes to the 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 the underlying bone, causing chronic pain and stiffness.
People with osteoarthritis have limited treatment options: pain relievers or joint replacement surgery.
Previous research had pinpointed two molecules, alpha-KLOTHO 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 extra-cellular matrix from degrading.
TGFβR2 acts more directly on cartilage cells, stimulating their proliferation and preventing their breakdown.
While each drug alone had only moderately curbed osteoarthritis in animal models of the disease, the team wondered if the two drugs would act more effectively in concert.
The researchers treated young, otherwise healthy rats with osteoarthritis with viral particles containing the DNA instructions for making αKLOTHO and TGFβR2.
Six weeks after the treatment, rats that had received control particles had more severe osteoarthritis in their knees, with the disease progressing from stage 2 to stage 4.
However, rats that had received particles containing αKLOTHO and TGFβR2 DNA showed recovery of their cartilage: the cartilage was thicker, fewer cells were dying, and actively proliferating cells were present.
These animals’ disease improved from stage 2 to stage 1, a mild form of osteoarthritis, and no negative side effects were observed.
To test the applicability of the drug combination to humans, the team treated isolated human articular cartilage cells with αKLOTHO and TGFβR2.
Levels of molecules involved in cell proliferation, extra-cellular matrix formation, and cartilage cell identity all increased.
The research team plans to develop the treatment further, including testing whether soluble molecules of the αKLOTHO and TGFβR2 proteins can be taken directly,
They also will study whether the combination of drugs can prevent the development of osteoarthritis before symptoms develop.
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