Osteoarthritis (OA) is a common disease that affects 30 million adults in the United States. OA is a disease of the entire joint, involving the cartilage, joint lining, ligaments and bone.

But OA is more than joints just wearing out. The disease is characterized by cartilage breakdown, bony joint changes, tendon and ligament deterioration, and various degrees of inflammation of the joint synovium. Now, researchers are looking at the role that specific proteins play in joint health.

Aging is a risk factor for OA, which most often affects middle-age to elderly people. The disorder most often affects hands and weight-bearing joints such as knees, hips, feet and the back, but it can affect almost any joint in the body. Symptoms range from mild to severe, and 43.5 percent of adults with physician-diagnosed OA have limitations in their usual activities related to their arthritis.

The goal of treatment in OA is to reduce pain and improve function. The outcome of OA depends on which joints are involved and the rate of disease progression. Treatment can usually be effectively managed with lifestyle changes, physical therapy, medication and surgery.

Exercise is an important part of treatment, because it can decrease joint pain and improve function. Treatment also may involve topical pain relievers or nonsteroidal anti-inflammatory drugs. Currently, the process underlying osteoarthritis cannot be reversed, but researchers are trying to find ways to at least slow or maybe reverse this joint damage.

A new study from scientists at The Scripps Research Institute (TSRI) demonstrates why the risk of OA increases with age and offers a potential option for developing new therapies to maintain healthy joints. Martin Lotz, M.D., a TSRI professor and senior author of the study discovered that FoxO proteins control the expression of genes that are essential for maintaining joint health.

FoxO proteins are transcription factors that regulate autophagy, metabolism and aging. Lotz has previously shown that as joints age, levels of FoxO proteins in cartilage decrease and that people with OA have a lower expression of the genes needed for autophagy.

For the new study, researchers used mouse models with FoxO deficiency in cartilage to see how the FoxO proteins affect maintenance of cartilage throughout adulthood. They found that cartilage was thicker and chondrocytes were more proliferative in young mice lacking FoxO in cartilage.

FoxO-deficient mice exhibited worse arthritis with aging and increased cartilage degradation in response to surgically induced arthritis. They also expressed less lubricin, a protein that helps reduce friction in joints. FoxO1 and autophagy-related genes were reduced in human chondrocytes from patients with OA; restoring FoxO1 expression reduced inflammatory cytokines and up-regulated lubricin.

This study suggests that FoxO factors could be targets for therapy in osteoarthritis. The next step in this research is to develop molecules that enhance FoxO and test them in experimental models of OA.