Osteoarthritis is a very common age related disease that affects more than 30 million Americans. FoxO proteins have been suggested by this study to may be able to help to control healthy cells in the cartilage of the joints, with findings showing that FoxO transcription factors control the expression of essential genes.
With aging the amounts of FoxO protein in cartilage decreases in joints, it was also observed that low expression of the genes occurred in people with osteoarthritis needed for autophagy, which is the cell’s process to separate and reuse repaired structures to maintain health. Model mice were utilized in this study with the FoxO deficiency to diagnose the influence of the protein over cartilage through adulthood. A salient difference was observed in the knockout mice which was the degeneration of cartilage at an earlier age than the controlled mice, they also suffered from acute forms of post traumatic osteoarthritis caused by meniscus injuries, and these mice underwent treadmill running which exposed these mice to the damage of the cartilage. Deficient mice had autophagy deficiency and some defects in the process which is involved in protecting cells from injury by oxidants. Cartilage in these mice did not get enough lubricin that usually secures the cartilage from friction and wear, which is also related to a loss of healthy cells in superficial zone a cartilage layer of the knee.
FoxO proteins working as transcription factors to control gene expression was at the root of all these problems. In the absence of the proteins the expression of inflammatory related genes escalates causing pain and a rapid decrease in levels of autophagy related genes preventing cells from repairing themselves. It was noted that the internal mechanisms keeping cells healthy are not involved with these knockout mice.
Continued research is required to develop molecules that improve FoxO and evaluate them in experimental models of osteoarthritis.
