Fight Aging!

Researchers here present an interesting view of how chronic inflammation affects cartilage tissue to cause the progression of osteoarthritis. A feedback loop is established between mechanisms of inflammation and mechanisms of pressure sensing, leading to the outcome of cartilage degeneration. Novel points of intervention will no doubt arise as the result of this work, with researchers seeking to break the feedback loop. The best approach still appears to be prevention of the chronic inflammation of aging, given the degree to which rising inflammation contributes to myriad age-related conditions.

An unfortunate biological "feed-forward" loop drives cartilage cells in an arthritic joint to actually contribute to progression of the disease. Cartilage is the highly lubricated, low-friction, elastic tissue that lines joint surfaces, cushioning movements and absorbing millions of cycles of mechanical compression. As cartilage breaks down in painful osteoarthritis, the ends of bones can come together bone-on-bone, increasing pain even more.

The cells that build and maintain cartilage are called chondrocytes, and on their surface can be found ion channels that are sensitive to force, called Piezo1 and Piezo2. In response to mechanical loads on the joint, Piezo channels send signals into the cell that can change gene activity in that cell. Normally, chondrocytes produce extracellular matrix, the structural proteins and other biomolecules that give cartilage its mechanical stiffness, elasticity and low friction. But in osteoarthritis, degeneration and malfunction of these cells - which are incapable of repair by cell division - contribute to the progressive breakdown of cartilage.

One of the other hallmarks of osteoarthritis is chronic, low-grade inflammation, driven by a signaling molecule called interleukin-1 alpha. Using cartilage cells from pigs and from human joints removed for replacement surgeries, the researchers wanted to see how inflammation affects chondrocytes. They found that interleukin signaling tells the cell to produce more Piezo channels, making the cell even more sensitive to pressure and resulting in what the researchers call a harmful 'feed-forward' loop that leads to more breakdown of the cartilage. "Interleukin reprograms the chondrocytes so that they're more sensitive to mechanical trauma. The feed-forward cycle slowly grinds them down and the cell cannot be replaced. It's cartilage reprogramming itself to do more damage."

Link: https://today.duke.edu/2021/03/inflammation-and-pressure-sensing-leads-%E2%80%98feed-forward%E2%80%99-loop-osteoarthritis