How patients can be motivated to get appropriate exercise despite pain, what role exercise plays with regard to the knee across different ages, and what processes take place at the molecular biology level are being studied in a project by the DynAge Focus Area at Freie Universität. DynAge is a research alliance between Freie Universität and Charité dealing with disease over the course of a person’s lifespan.

The knee carries the heaviest load of all of the joints in the body – which means that signs of wear set in as people age. Symptoms are worse in those with improper posture and the improper distribution of weight that goes with it – such as in those with knock knees or bow legs and patients who have suffered an injury to the anterior cruciate ligament (ACL) or the meniscus. Being overweight is also a risk factor: With every additional kilogram, the mechanical pressure on the joints rises, and with it the risk of inflammation. If too much or too little pressure is placed on the cartilage in the joint, it degenerates and ceases to perform its cushioning and lubricating functions. The bones rub against each other, causing severe, chronic pain.

Alongside negative effects on quality of life for those afflicted with this condition, arthritis of the knee also carries a huge social cost. “In Germany alone, the costs of treatment and consequences come to about three billion euros per year,” says Wolfgang Ertel, a professor of trauma surgery at Charité – Universitätsmedizin Berlin and director of the Department of Traumatology and Reconstructive Surgery at the Benjamin Franklin campus. He points out that early prevention is key in terms of avoiding the need for pain medications and surgery later on.

Together with Professor Dieter Felsenberg, the head of the Musculoskeletal Research Center Berlin (MRCB), which is likewise located on the Benjamin Franklin campus, Ertel is involved in a new project focusing on muscle exercise using a vibration unit developed specifically for medical purposes. The device makes it possible to develop muscle extremely rapidly, an effect that has been tested in settings including in space medicine studies performed by the European Space Agency (ESA). “We know from the studies that the more exercise the surrounding muscle has received, the less susceptible the bone is to osteoporosis,” Felsenberg says. “We are now studying the interactions between muscle and cartilage with an eye to slowing or even halting the degeneration of cartilage in the knee joint,” he adds.

Disorders of the Knee Carry Heavy Social Costs

The researchers’ hypothesis is that targeted mechanical exertion trains the muscle and boosts the supply of nutrients to the cartilage. In patients with arthritis and the cartilage damage that goes with it, Felsenberg says, there is always a disruption in the situation with the supply of nutrients to the cartilage. “The cartilage always needs to be pressed and squeezed, which distributes nutrients and cell information,” he points out.

Ertel and Felsenberg plan to work with researchers from the Focus Area to find out how, exactly, this supply to the cartilage occurs. The researchers are moving into uncharted territory with this line of inquiry. “We know from a number of studies how important exercise is to joints,” Ertel says. “But what we don’t know is which messengers ensure that the stem cells that regenerate the cartilage are produced.” Plans call for this to be studied over the next four years, with a total of five million euros in funding from the German Federal Ministry of Education and Research (BMBF). “We will start putting together the participants in the study in the spring of 2015, and training is scheduled to start in the summer,” Ertel says. Participants will be required to do various things, including undergoing two orthopedic “mini-interventions,” the orthopedist says. “A sample of muscle tissue will be taken from the calf once, and another time we will take a sample of cartilage and joint capsule tissue.”

The tissue samples will go to Professor Petra Knaus, of the Institute of Chemistry and Biochemistry at Freie Universität Berlin, who is researching the connections between biomechanical and biochemical signals with her team. Based on the data gleaned from the samples, Stephan Zachow, of the Zuse Institute Berlin (ZIB), and Max von Kleist, of the Department of Mathematics and Computer Science at Freie Universität, will create three-dimensional models of things like the cartilage covering the joint. Participation in the study is limited to patients with moderate arthritis who suffer chronic pain, but whose cartilage is not yet completely destroyed.

Another important factor is that participants must live in the Berlin area, as they will be asked to exercise under a doctor’s supervision there as many as three times a week and then spend another year afterward following an exercise regimen on their own. Will their motivation last that long? That is where the health psychologists on Nina Knoll’s team come in. They are studying what overall conditions must be created to keep patients on the ball when it comes to exercise. Ertel is confident. “People who are in pain and then see that with regular exercise, their pain diminishes, exercise voluntarily,” he says.