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Credit: https://www.chrisbaileyorthopaedics.com/blog/warning-signs-for-osteoarthritis/

Researchers create newly engineered cartilage that protects itself from inflammation

March 24, 2021

A research team from Washington University has developed newly engineered cartilage cells in pigs that produce an anti-inflammatory molecule when stressed.
The molecule, IL-1Ra, helps maintain structural integrity and strength to cartilage that is under stress or compression.
Not only could this strategy be helpful in the treatment of osteoarthritis, but these programmed cells could also be modified to deliver therapies in relation to a variety of medical conditions.

A research team lead by Dr. Farshid Guilak from Washington University in St. Louis has been testing whether cartilage cells could be engineered to protect themselves from inflammation. During the study, the team managed to alter cartilage cells from pigs; which when stressed, produce an anti-inflammatory molecule. The study was funded in part by NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute on Aging (NIA), and the National Center for Advancing Translational Sciences (NCATS). The results of the study were then published in the journal, Science Advances. Naturally, the joints in our knees and hands rely on cartilage tissue to stop the bones from rubbing together. But as we age, the wear and tear over a lifetime can cause cartilage to break down. This leads to a painful condition known as osteoarthritis. Some of the major symptoms of osteoarthritis include stiffness, joint pain, and swelling. In fact, more than 30 million Americans today suffer from the condition. And the worst part is, there is no treatment in place to prevent or reverse the condition’s progression. However, this hasn’t stopped researchers from toying with the prospect of growing new cartilage in labs that could be implanted into these joints. Joints that are riddled with arthritis usually contain many molecules that cause chronic inflammation. This inflammation—coupled with the physical stress caused by normal and regular movement—can destroy replaced cartilage fast. To address this, the research team first identified a protein called TRPV4 in the membrane of cartilage cells. This protein detects alterations within the cells when they are under compression. The research team also discovered that TRPV4 can be triggered either by a change of fluid in the cells through a process called osmotic loading, or through the effects of mechanical forces. The team also noted that in response, TRPV4 triggered specific genetic pathways in cartilage cells associated with inflammation and metabolism. To advance their study, the researchers modified these genetic circuits to create an anti-inflammatory molecule known as interleukin-1 receptor antagonist (IL-1Ra). And the cells with these specific circuits were then modified to form cartilage. When these newly engineered cells were exposed to either osmotic loading or mechanical forces, they produced IL-1Ra. The duration and timing of production relied on which genetic circuit was used. This therefore implied that production could be customized by harnessing the different cellular pathways that turn on and off at different times. In the final parts of the study, researchers then tested whether the production of IL-1Ra could protect cartilage cells in an inflammatory environment; similar to that of patients exhibiting osteoarthritis. They exposed the engineered cartilage to osmotic loading as well as an inflammatory molecule for three days. By the end of the test period, the team observed that the cartilage that did not produce any IL-1Ra gradually broke down. As for the engineered cartilage, it produced the molecule that maintained its structural integrity and strength. The publication of these findings are critical to the treatment of osteoarthritis, as they demonstrate the possibility to engineer living tissue to be able to produce its own therapeutic drugs. Not only could this strategy be helpful in the treatment of osteoarthritis, but these programmed cells could also be modified to deliver therapies in relation to a variety of medical conditions.

References: https://www.nia.nih.gov/news/engineered-cartilage-produces-anti-inflammatory-drug

Researchers create newly engineered cartilage that protects itself from inflammation

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