Results from a study conducted at The Scripps Research Institute (TSRI) provide new insight into why osteoarthritis risk increased with age, and the findings may inform the development of new treatments to preserve joint health. Researchers found that certain proteins are associated with the maintenance of healthy cells in cartilage, and that levels of these proteins tend to decline with advancing age. Previous research conducted by the TSRI team found that osteoarthritis sufferers also have reduced expression of the genes controlling autophagy, the process by which cells address damage and repair themselves. Senior author and TSRI professor Martin Lotz, PhD, summarized "We discovered that FoxO transcription factors control the expression of genes that are essential for maintaining joint health. Drugs that boost the expression and activity of FoxO could be a strategy for preventing and treating osteoarthritis." The findings were published earlier this week in the journal Science Translational Medicine.
In the study, mice with FoxO deficiency in their cartilage were compared to a control group of normal mice to assess ability to maintain cartilage throughout adulthood. The FoxO deficient mice exhibited faster cartilage degeneration, more severe osteoarthritis from injury, and greater susceptibility to cartilage damage from treadmill running than did the control cohort. Researchers found that FoxO proteins are involved in the regulation of gene expression, and deficiency resulted in overexpression of inflammation related genes and under expression of autophagy related genes. According to the authors, a goal of future research is to develop new molecules that enhance FoxO and test these for efficacy in treating osteoarthritis.
Read a news story about the findings.
The journal abstract may be read here.
Posted on February 15, 2018