According to significant new study published in the journal Science
Advances, a hitherto unstudied protein in the framework of osteoarthritis
may be crucial in the disease's prevention, which featured work by Justin
Parreno, an assistant professor at the University of Delaware.
Osteoarthritis is an incurable, painful, and debilitating joint ailment
caused by the disintegration of the cartilage that cushions the ends of the
bones, known as articular cartilage. It is the most prevalent kind of
arthritis, affecting more than 32.5 million Americans, according to the
Centers for Disease Control and Prevention. It most commonly arises in the
hands, knees, or hips.
Parreno discovered that the protein adseverin helps maintain articular
cartilage healthy as a doctorate student at the University of Toronto. This
is the first time a particular protein related with cell structure has been
identified as being osteoarthritic-protective.
The finding happened virtually by chance. Parreno and his colleagues were
working on another cartilage treatment when he discovered that healthy
cartilage cells have a lot of adseverin but damaged cartilage cells don't.
Adseverin concentration eventually influences the structural scaffolding of
cells, known as filamentous(F) actin.
F-actin protects cartilage cells from the pressures that occur when the
joints move. Cells eventually perish when they lose F-actin.
"The cells are really round, and you have F-actin around the cells," said
Parreno, a member of the University of Delaware's Department of Biological
Sciences. "If F-actin is lost, those cells become sensitive due to
mechanical stress, and they will most likely die." Dead cells are unable to
synthesize the chemicals needed to rebuild cartilage, and the cartilage
gradually dissolves."
Not only do the cells die, but the surviving cells begin to generate
chemicals that wreak havoc on the cartilage.
"The cells that remain are also producing hypertrophic molecules, resulting
in mineralization and tissue stiffness, which leads to a really bad joint,"
Parreno explained.
Current therapies for osteoarthritis either require surgery or focus on
pain management. While Parreno acknowledges that the research has not been
tested in humans, he believes the discoveries may pave the way for therapies
that target the protein.
"If we can maintain the levels of adseverin, or alternatively find a way to
keep that F-actin at a high enough level, we might be able to prevent cell
death," he added. "We've got to keep these cells alive and healthy."
Through the Delaware Center for Musculoskeletal Research (DCMR), Parreno's
group at UD continues to explore the control of F-actin and its link to
osteoarthritis processes, including cell death. Tropomyosin, another
F-actin-binding protein, is being studied in the lab. According to Parreno,
F-actin may be the key to controlling cartilage degradation.
"What I find really groundbreaking about this work is not necessarily the
adseverin, but the fact that F-actin is reduced in osteoarthritis and leads
to all of these changes," Parreno said. "We know all of these changes are
taking place, and if we can figure out what the critical node is in
regulating all of these things, we might be able to develop an
osteoarthritis therapy." I believe that targeting F-actin might be that, and
we have only scratched the surface.
"Adseverin regulates F-actin, but so do other molecules, so we need to know
if it is the main molecule or just one of them." Once we know which
molecules are critical, we might be able to chemically target them to avoid
joint destruction."
It might also be the key to other difficulties in the musculoskeletal
system. Parreno is also a member of an interdisciplinary research team that
is looking at multi-scale tendon injury and aberrant cellular responses in
tendinopathy. Parreno is exploring the role of F-actin in the regulation of
tendinosis as part of this work.
Dawn Elliott, Blue and Gold Distinguished Professor of Biomedical
Engineering within the College of Engineering and DCMR director, leads the
team, which also includes co-investigator Karin Grävare Silbernagel,
professor of physical therapy in the College of Health Sciences. The
National Institutes of Health awarded the group a nearly $2.3 million,
five-year R01 Grant last October.
The study of osteoarthritis is somewhat personal for Parreno. He has been
injured as an athlete who grew up playing hockey and now plays basketball
and does weights at the Carpenter Sports Building (Little Bob). "I've always
been interested in the musculoskeletal system because of sports." Because of
this, I believe I was predisposed to orthopedic research. So it's somewhat
self-serving. "I know I'm going to get osteoarthritis," he joked.
