Osteoarthritis is a common disorder that typically affects older people. It occurs when the cartilage in joints break down, causing pain and stiffness that worsens over time.
“There is no cure for osteoarthritis, and we don’t have many treatment options besides pain management and joint replacement, which is expensive and invasive,” said Van Andel Institute’s Dr. Tao Yang. “There is a critical need to understand how and why osteoarthritis develops and how aging influences that process.”
As a scientist who studies bone biology, Yang is keen to understand how osteoarthritis arises and progresses.
Unlike bone, cartilage cannot repair itself. That means Yang must seek out other opportunities to slow osteoarthritis progression and fix damaged tissue.
In a recent study published in the journal Osteoarthritis and Cartilage, Yang and his team describe for the first time a mechanism that may explain how aging promotes osteoarthritis development — and it involves old viruses called endogenous retroviruses (ERVs).
ERVs are remnants of ancestral viruses that long ago became part of our DNA. Many ERVs are “silenced” by epigenetic marks, which are chemical tags that keep parts of our DNA dormant. Loss of these marks can cause the ERVs to become active and, in some cases, contribute to disease.
To understand the role of ERVs in osteoarthritis, Yang and his lab compared damaged and healthy cartilage samples. Their in-depth analysis revealed a striking pattern: increased ERV activation in damaged cartilage.
“As we age, we lose the mechanisms that keep these old viruses silenced,” Yang explained. “This stimulates an immune response, which causes inflammation that makes osteoarthritis progress.”
The study marks the first direct link between aging, osteoarthritis development and ERV activation. It suggests that re-silencing ERVs may suppress inflammation and slow down osteoarthritis progression.
But the idea of investigating ERVs did not come out of the blue. Initially, Yang was inspired by other VAI research on ERVs in different disease settings. The study resulted from a collaboration with VAI Fellow Dr. Josh Jang, who studies ERVs in cancer. A growing body of research has implicated ERVs as players in inflammation and aging but, until Yang’s study, there was little known about ERVs in osteoarthritis.
“Our next step is to look at how to silence ERVs,” Yang said. “If there is a way we can quiet down inflammation, it may help slow down joint aging and osteoarthritis progression.”
Other authors include Ye Liu, Ph.D., Vladimir Molchanov, Yaguang Zhao, Ph.D., Di Lu, Ph.D., Haudie Liu, Ph.D., and H. Josh Jang, Ph.D., of Van Andel Institute.
Research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health under award nos. R01AG083568 (Yang and Wang) and R01AG061086 (Yang). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.