Osteoarthritis: Novel Cartilage Cells Release Drug When Stressed

To develop new treatments for osteoarthritis, researchers have genetically engineered cartilage to deliver an anti-inflammatory drug in response to activities similar to the bending of a knee or other motions that put stress on joints. The research conducted by Washington University School of Medicine in St. Louis, is published in the journal Science Advances.

One of the early symptoms of osteoarthritis is pain in response to motion like movements that involve the so-called mechanical loading of a joint. Normal activities are hampered by joint pain that accompanies bending or lifting.

In the laboratory, the researchers altered genes in the cartilage cells and programmed them to respond to the mechanical stress associated with movement and weight-bearing by producing a drug to combat inflammation.

Senior Investigator Farshid Guilak PhD, Mildred B. Simon Professor of Orthopaedic Surgery said, “Drugs such as ibuprofen and naproxen that ease joint pain and lower systemic inflammation are the main treatments for osteoarthritis pain, but there are no therapies that actually prevent damage in the joints of patients with this debilitating form of arthritis. We’ve developed a new field of research called mechanogenetics, where we can engineer cartilage cells to respond to the mechanical loading of the joint. Every time cells are under that stress, they produce an anti-inflammatory, biologic drug to reduce inflammation and limit arthritis-related damage.”

The researchers first conducted experiments in the lab using cartilage cells from pigs to understand how those cells sense when they are being mechanically stressed. They were able to identify key pathways in the cells that respond to stress and the genes in the cartilage that are activated by mechanical loading.

Similar to the touch sensor on a smart phone, the cartilage cells were able to detect when stress is being applied and the inflammation associated with the excessive stress of arthritis causes cartilage to break down. The cells in these experiments responded to the stress by secreting an anti-inflammatory drug that blocked cartilage damage.

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The researchers altered the DNA in the cells to sense the load and respond accordingly to make anti-arthritis drug.

The cells were engineered to release a drug called anakinra (Kineret) which is an interleukin-1 receptor antagonist. The drug is used to treat rheumatoid arthritis and is a promising treatment for post-traumatic osteoarthritis that occurs following joint injury. Earlier studies with anakinra (Kineret) in patients with osteoarthritis have shown it to be safe but ineffective when only injected into a joint one time.

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In order to work well, the drug needs to be released in arthritic joints over longer periods. He said, “This drug doesn’t seem to work unless it’s delivered continuously for years, which may be why it hasn’t worked well in clinical trials involving patients with osteoarthritis. In our experiments in cells in the lab, we used existing signaling systems in the cartilage cells that we engineered so that they would release the drug whenever it’s needed. Here, we are using synthetic biology to create an artificial cell type that we can program to respond to what we want it to respond to.”

Along with reducing inflammation in arthritic joints, specific cartilage cells deliver the drug only when and where it’s needed. This avoids side effects associated with long-term delivery of a strong anti-inflammatory drug to the entire body.

The team also plans to use the same technique to alter other types of cells to make different drugs. Guilak said, “We can create cells that automatically produce pain-relieving drugs, anti-inflammatory drugs or growth factors to make cartilage regenerate. We think this strategy could be a framework for doing what we might need to do to program cells to deliver therapies in response to a variety of medical problems.”

Source-Medindia