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Fitness & Exercise for Senior Citizens
Researchers Say It's Smurfs Causing Your Knee to
Ache, May Predict Arthritis
Half with knee injury will later go on to develop
osteoarthritis
 Oct.
22, 2007 - 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.
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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.”
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Why Your Knee Hurts |
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The location of knee pain can help identify the problem.
Pain on the
front of the knee can be due to bursitis, arthritis, or softening of the
patella cartilage as in chondromalacia patella.
Pain on the sides of the
knee is commonly related to injuries to the collateral ligaments,
arthritis, or tears to the meniscuses.
Pain in the back of the knee can
be caused by arthritis or cysts, known as Baker’s cysts. Baker’s cysts
are an accumulation of joint fluid (synovial fluid) that forms behind
the knee.
Overall knee pain can be due to bursitis, arthritis, tears in
the ligaments, osteoarthritis of the joint, or infection.
Instability, or giving way, is also another common knee problem.
Instability is usually associated with damage or problems with the
meniscuses, collateral ligaments, or patella tracking.
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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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