The ‘Wonder Tissue’

“The diagnosis of OA is related to cartilage, the ‘wonder tissue,’” began Linda Sandell, PhD, professor and director of research at the Center for Musculoskeletal Research at the Washington University School of Medicine in St. Louis, “but not all cartilage is the same.”

Sandell’s lab wondered if some people have the ability to repair cartilage and whether it is inherited. Using large- and small-inbred mice strains, healing from mouse ear wounds and knee joint injuries were observed over time. It was determined that cartilage regeneration is inherited (large mice strains healed, while small did not), and this visible characteristic is related to ear wound healing.

Going a step further, Sandell – who is also the president of the Osteoarthritis Research Society International (OARSI) – wondered if OA in mice can be predicted by the ability to repair cartilage. Studies in her lab showed that healers appeared to have protection from OA (i.e., they did not get severe cartilage degeneration) versus the non-healers who developed OA. In one strain, subchondral bone became thinner early but regenerated in late stages post-surgery. “This shows that bone changes occur in response to injury and cartilage degeneration,” she concluded.

Conditions that Lead to OA

Studies have shown that ACL injury leads to OA 10 to 15 years later in 50 percent of cases. The negative effects of obesity, abnormal physiology and age on the development of OA were also addressed in “Disease Mechanisms that Impact the Joint.” “Overweight adults exert greater loads while walking because they must stabilize a greater mass,” said Steve Messier, PhD, professor at Wake Forest University in Winston-Salem, N.C., “and abnormal stress can cause mechanical failure and disability in joints.”

More than 450 adults older than 55 years old with a body mass index greater than 27 took part in the Intensive Diet and Exercise for Arthritis (IDEA) study for 18 months. Messier wanted to determine if there is a non-drug, noninvasive solution to reduce loads and relieve pain.

Participants were divided into three intervention groups: exercise only (walking and weight training), diet (800 to 1,000 kilocalories per day) combined with group counseling, and a combination of exercise and diet. Not surprisingly, all groups experienced reduced pain and improved function, but those who lost more than 10 percent of their body weight experienced even less pain and more function. Measurements of systemic inflammatory biomarker IL-6 were reduced in both diet groups, indicating a decreased risk of disability.

John Hardin, MD, vice president of research for the Arthritis Foundation, summed it up by saying, “Most importantly we learned that exercise is not just a mechanism to use up more calories, but actually adds an additional factor to symptom improvement beyond reduction in mechanical stress.”

Future of OA Research

An exciting area of research that will continue to develop is stem cell and regenerative medicine. Chondrogenesis is a process that uses unspecialized stem cells to grow cartilage tissue via nanotechnology. Rocky Tuan, PhD, professor at the University of Pittsburgh Medical Center, presented his recent research involving growing cartilage on a microscopic tissue-based structure to use directly on a femoral bone in a live animal model. The long-term goal is to grow tissue and other biomaterials to rebuild or replace cartilage.

Mother Nature had different plans for the conclusion of the SNOW V conference, as many attendees needed to leave early due to Hurricane Sandy. It precluded the call for applications for the ACL Intervention Initiative, a multicenter feasibility study sponsored by the Arthritis Foundation that uses ACL injury as a model for investigating chemical and imaging biomarkers as they relate to predicting OA. This is an important step in showing that images and data from several different locations can be standardized. The Arthritis Foundation will work with the partnering institutions to carry out this two-year project, estimated to cost $1 million.