The molecular pathway that responds to zinc levels in cartilage cells is responsible for osteoarthritis-related tissue damage, according to the published report in the journal Cell Press.
Osteoarthritis destroys joint cartilage tissue and is a leading cause of disability. With the discovery of the protein ZIP8, which transports zinc into these cells and sets the stage for cartilage breakdown, more effective therapies can be implemented in individuals living with osteoarthritis.
Senior study author Jang-Soo Chun of the Gwangju Institute of Science and Technology says this study represents a completely novel concept.
"No evidence available to date clearly indicated that zinc plays a causal role in osteoarthritis," she revealed in a statement. "In our study, we revealed the entire series of molecular events in the osteoarthritis zinc pathway, from zinc influx into cells to cartilage destruction."
What older adults feel as pain due to osteoarthritis is really their bones rubbing together, causing not only pain but also swelling and stiffness. Cartilage cells produce proteins called matrix-degrading enzymes that destroy the extracellular matrix of the tissue. That these enzymes need zinc to function is what led researchers to take a closer look at the mineral in the first place.
The cartilage from osteoarthritis patients was examined and a mouse model of the disease used as well.
Researchers found abnormally high levels of the protein ZIP8, which is involved in transporting zinc from the outside environment to inside the cartilage cells. The influx of zinc via ZIP8 activated another protein, metal-regulatory transcription factor-1 (MTF1), which then increased matrix-degrading enzyme levels in the cartilage cells. This series of events, referred to as the zinc-ZIP8-MTF1 pathway, is the key to osteoarthritis-related cartilage destruction, as demonstrated in their mice experiments.
"We are hopeful that this research will lead to the discovery and rapid development of novel drugs to suppress the progression of this debilitating disease," Chun said about their findings.
