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SMURFs
May Be Responsible For Aching Knees
19
Oct 2007
As
edited by Joint-Pain-Forum.com
A
new clinical trial seeks to predict who is most likely to experience
osteoarthritis, and to test whether an experimental treatment can
prevent it altogether. Physicians are setting their sights on people
who sustain a knee injury, seeking to understand why nearly half of
them will later go on to develop osteoarthritis, a debilitating
condition that causes pain and disability in more than 20 million
Americans each year.
The work is funded by a
special class of National Institutes of Health grants awarded to
research programs that show promise of quickly translating basic
science discoveries into patient treatments. In this case, initial
research has shown that an enzyme which controls the response of cells
to growth factors may in fact be a major cause of osteoarthritis. The
enzymes are called "Smad Ubiquitination Regulatory Factors," or,
smurfs, but unlike the small, loveable blue cartoon characters,
researchers believe that a particular form of these regulatory enzymes,
smurf2, might in fact be responsible for America's leading cause of
disability.
"We believe that smurf2 controls
whether or not a cartilage cell matures and calcifies into hard bone,
which is a very good thing when 'turned on' in those areas of the body
where we are supposed to have hard bone," said Randy Rosier, M.D.,
Ph.D., professor of Orthopaedics and director of Research Translation
in Orthopaedics at the University of Rochester Medical Center. "But
when smurf2 is active in joint cartilage, it may set off a chain
reaction that leads to the steady deterioration of the smooth gliding
surface tissue, or cartilage, which comprises the joint surface. When
this occurs, the cartilage breaks down and severely damages the
weight-bearing surface of a joint. Or, put another way, activation of
smurf2 in the joint cartilage appears to significantly contribute to
the onset of osteoarthritis."
----------------------------
Article
adapted by
www.Joint-Pain-Forum.com from original press release.
----------------------------
Frog Embryos and Cartilage
Cells
Over the past decade, smurfs have
begun to capture the attention of scientists, after a research team led
by Gerald H. Thomsen, Ph.D., at Stony Brook University, identified the
enzymes' critical role in regulating levels of important molecules that
help determine which genes are turned on or off in a variety of cells
throughout the body. In fact, Rosier first became intrigued with smurfs
after reading about how they helped cell differentiation in frog
embryos.
"I got to wondering what, if any, control
smurfs might have on cartilage cell development and maturation," he
said.
And so, over the course of several years,
Rosier and his research team conducted a series of experiments that not
only identified the role of smurf2 in bone cell and cartilage
signaling, but uncovered its vital link to osteoarthritis.
First,
the team compared healthy and diseased cartilage, and discovered that
smurf2 was only present in osteoarthritic cartilage. They next
demonstrated that smurf2s are stimulated by inflammation, and are
expressed in cartilage within a few months following an injury.
Further
experiments showed that smurf2 was present in the joints of patients in
early-stage arthritis, when patients might begin to experience mild
discomfort, but long before other well-known molecular markers of
osteoarthritis began to emerge.
"It was at this
point that we knew smurf2s are not just a casual bystander in
arthritis, but rather, the catalyst that sets off the chain reaction
that leads to osteoarthritis," Rosier said
Rosier
is now teaming with sports medicine surgeon Michael Maloney, M.D., to
conduct the just underway clinical trial. The team will examine tissue
samples from healthy, non-arthritic patients who have sustained an
injury to the meniscus to determine the level of smurf2 expression in
their cartilage at the beginning of the trial. In addition, a baseline
MRI will measure the cartilage at the point of injury, and three years
later. If results confirm the team's earlier findings, the MRIs of
patients with high smurf2 expression will show the beginning signs of
osteoarthritis as measured by hardening of the cartilage and bone loss.
"Our ultimate goal is to create a simple diagnostic
test to determine whether a person with a knee injury has a high level
of smurf2s in their cartilage," Rosier said. "In these cases,
physicians can advise the patient to stop high-intensity, wear-and-tear
activity, slowing the onset of arthritis and lessening its severity.
Eventually, we hope to create an injection that will stop smurf2s'
ability to turn on the calcification and degeneration process in
cartilage that leads to osteoarthritis."
While
Rosier admits the development of an injection is a long time off, he
believes that physician counseling will do a world of good and that's
good news for a disease that is estimated to cost the United States
about $42 billion a year.
"Think of a 25-year male
old who tears his meniscus. Today, after successfully removing the torn
meniscus fragment and physical therapy, in most cases, he's right back
to his regular activity level," Rosier said. "But if his physician can
tell him with certainty that he will develop osteoarthritis, he has the
opportunity to change his activity level, reducing his risk and
severity of osteoarthritis."
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