Is zinc the missing link for osteoarthritis therapies?

February 13, 2014, Cell Press

Osteoarthritis is a leading cause of disability, characterized by the destruction of cartilage tissue in joints, but there is a lack of effective therapies because the underlying molecular causes have been unclear. A study published by Cell Press February 13th in the journal Cell reveals that osteoarthritis-related tissue damage is caused by a molecular pathway that is involved in regulating and responding to zinc levels inside of cartilage cells. A protein called ZIP8 transports zinc inside these cells, setting off a cascade of molecular events that result in the destruction of cartilage tissue in mice. The findings could lead to a new generation of therapies for osteoarthritis.

"No evidence available to date clearly indicated that zinc plays a causal role in osteoarthritis," says senior study author Jang-Soo Chun of the Gwangju Institute of Science and Technology. "In our study, we revealed the entire series of molecular events in the osteoarthritis zinc pathway, from zinc influx into cells to cartilage destruction."

When the cartilage breaks down in osteoarthritis, the bones rub together, causing pain, swelling, and stiffness. This is caused by proteins called matrix-degrading enzymes, which are produced by cartilage cells and are the key culprits responsible for degrading the extracellular matrix—the structural support system that surrounds cells and holds them together. Because matrix-degrading enzymes require zinc to function, Chun and his team suspected that zinc levels inside of cartilage cells may play a role in osteoarthritis.

To test this idea, the researchers first examined cartilage from osteoarthritis patients as well as a mouse model of the disease. They found abnormally high levels of a protein called ZIP8, which is embedded in the plasma membrane of cartilage cells and is involved in transporting zinc inside of these cells from the outside environment. Zinc influx through ZIP8 activated a protein called metal-regulatory transcription factor-1 (MTF1), which in turn increased levels of matrix-degrading enzymes in . Through genetic experiments in mice, the researchers showed that this zinc-ZIP8-MTF1 pathway plays a key role in causing osteoarthritis-related cartilage destruction.

"Our findings suggest that local depletion of or pharmacological inhibition of ZIP8 function or MTF1 activity in would be effective therapeutic approaches for the treatment of ," Chun says. "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."

Explore further: Chemical signaling simulates exercise in cartilage cells

More information: Cell, Kim et al.: "Regulation of the catabolic cascade in osteoarthritis by the zinc axis." dx.doi.org/10.1016/j.cell.2014.01.007

Related Stories

Chemical signaling simulates exercise in cartilage cells

January 13, 2014
Cartilage is notoriously difficult to repair or grow, but researchers at Duke Medicine have taken a step toward understanding how to regenerate the connective tissue. By adding a chemical to cartilage cells, the chemical ...

Researcher provides insight into osteoarthritis

April 19, 2013
A researcher at The Feinstein Institute for Medical Research has discovered additional mechanical properties of articular cartilage, a protective cartilage on the ends of bones that wears down over time, resulting in the ...

Arthritis cartilage shows mitochondrial dysfunction

November 19, 2012
(HealthDay)—Cartilage from osteoarthritis patients shows greater oxidative damage and mitochondrial dysfunction than healthy cartilage, which is associated with the downregulation of the superoxide dismutase 2 (SOD2) gene, ...

Stem cell scientists first to track joint cartilage development in humans

December 13, 2013
(Medical Xpress)—Stem cell researchers from UCLA have published the first study to identify the origin cells and track the early development of human articular cartilage, providing what could be a new cell source and biological ...

Cartilage damaged from exercise may aid in early osteoarthritis detection

April 2, 2013
Osteoarthritis is the most common joint disorder, affecting about one-third of older adults, and currently there is no cure. A study published by Cell Press April 2nd in the Biophysical Journal reveals how the nanoscale biomechanical ...

Naturally occurring molecule in the body may have important consequences for treating osteoarthritis

July 11, 2013
UK scientists have found a naturally occurring molecule in the body which may have important consequences for treating osteoarthritis. Researchers from The University of Manchester and the University of Westminster have found ...

Recommended for you

Patchy distribution of joint inflammation resolved

November 16, 2018
Chronic inflammatory rheumatic diseases such as rheumatoid arthritis (RA) and spondylo-arthritis (SpA) are chronic, disabling diseases with a poor outcome for loco-motoric function if left untreated. RA and SpA each affect ...

Defense against joint degeneration

October 30, 2018
During cartilage development, chondrocytes secrete the extracellular matrix (ECM) and embed within the same environment. During progressive joint disease, such as osteoarthritis (OA), dysregulation of the process can lead ...

Becoming more sensitive to pain increases the risk of knee pain not going away

October 30, 2018
Becoming more sensitive to pain, or pain sensitization, is an important risk factor for developing persistent knee pain in osteoarthritis, according to a new study by researchers at Université de Montréal and its affiliated ...

Ground-breaking discovery finds new link between autoimmune diseases and a gut bacterium

October 29, 2018
Could microbes in our guts be sending out the wrong message? Queen's University Belfast researchers have, for the first time, found a specific microbe in the gut that pumps out protein molecules that mimic a human protein, ...

Research shows diet has little influence on precursor to gout

October 11, 2018
Dietary factors have a far smaller influence on urate levels (a precursor to gout) than previously envisaged, new University of Otago research reveals.

More doctor visits lead to less suicide attempts for fibromyalgia patients

September 19, 2018
Fibromyalgia patients who regularly visit their physicians are much less likely to attempt suicide than those who do not, according to a new Vanderbilt University Medical Center study published in Arthritis Care & Research.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.