ó Her foot pain began 15 years ago, leading to a 2002
diagnosis of osteoarthritis, which left her limping and unable
to walk for extended periods of time.
Deborah Cole Thomas, 60, of Plum, Pa., would undergo surgeries
to fuse joints in both feet along with a left-ankle
replacement, all from the wear-and-tear form of arthritis. She
endured shoulder pain and more recent problems with right-knee
pain, which she likens to a knife stab.
pain medications are a must.
try not to let it affect me," Thomas said, noting that
her husband, Llewellyn, 82, has had both arthritic knees
replaced. "It drives me to keep moving. I watched my mom
give up, and her hands became so crippled she had to be
now retired, worked as a Westinghouse computer engineer,
spending hours at a desk that made her "feel like the Tin
Man in ĎThe Wizard of Oz.í" Sheíd stand and
struggle to flex stiffened joints.
coming years, she faces further surgeries, including
knee-replacement surgery. But sheís still walking, with the
goal of 10,000 steps a day and an average of about 7,000.
wouldnít go to climb Mount Washington ó or Kilimanjaro,"
she said, adding that osteoarthritis can be immobilizing if
you let it.
canít run and isnít allowed to jump. Doctorís orders.
But she works around those limitations.
always something I can do just to keep moving."
people with osteoarthritis struggle to move, thereís plenty
of movement in research as scientists work through the
biological puzzle of osteoarthritis to come up with potential
University of Pittsburgh research team, led by Rocky S. Tuan
ó professor and executive vice chairman of the department of
orthopedic surgery and director of the Center for Cellular and
Molecular Engineering ó is making headway in understanding
the complex stew of enzymes (histones), proteins and genes
that cause osteoarthritis while identifying a potential
treatment to slow the rate of cartilage destruction.
further breaking news from the Tuan camp that sounds like
is using a 3-D printer, which makes structures one layer at a
time, to make new joints. Using a solution containing the
patientís stem cells, along with growth factors and
scaffolding material, the 3-D printer constructs actual
cartilage in the right shape to replace damaged cartilage.
stem-cell solution extruded through a catheter also could be
used to create new cartilage, as guided by a 3-D printer,
directly onto the joint bone.
tissue-engineered joints already have shown success in large
animals, raising the promise of creating replacement joints
for people now dependent on plastic and metal ones. The
process could be particularly useful in repairing battlefield
announced the success April 27 at the Experimental Biology
2014 scientific sessions and meeting in San Diego.
essentially speed up the development process by giving the
cells everything they need, while creating a scaffold to give
the tissue the exact shape and structure that we want,"
Tuan said, adding that his team continues working to develop
cartilage more closely resembling human cartilage.
joint replacements involving plastic and metal joints work
well, but they donít last long enough," Tuan said.
"For someone who is 60, thatís OK. But if you are in
your 30s, thatís not good because you may need revision
are not in position to say that it will last a lifetime. Time
is the true test," Tuan said of the tissue-engineered
joints his team has created. "I can only say itís very
promising and is looking good."
the business end of bones, include a covering made of flexible
and protective cartilage to prevent damage from friction. But
chronic wear and tear from overuse, traumatic injury or bone
misalignment, among other factors such as obesity, promotes a
biological process, not yet fully understood, that degrades
represents 80 percent of all cases of arthritis, whose various
forms plague 27 million Americans, making arthritis the nationís
major form of physical disability. The disease burden is
particularly acute in the aged population, with one out of two
individuals older than 65 having at least one joint affected.
promising University of Pittsburgh research, Tuan and Dr.
Veronica Ulici, an Arthritis Foundation-supported
post-doctoral fellow at the university and medical doctor, are
focusing on a method to prevent destruction of the cartilage,
which would do away with the need to replace joints.
joint is a very interesting organ," Tuan said.
"There is no blood flow there, or nerves."
immune response in the joint that occurs from chronic wear and
tear or injury increases the level of unhealthy inflammation,
which eventually causes cartilage degradation. Tuan said,
"It tries to repair itself, but in the end it
doctor of biochemistry and cell biology, and Ulici have
investigated the process, which focused attention on the
histone deactetylase enzymes, or HDAC.
to the joint activates certain genes to produce known
inflammatory factors, which increase the activity of
degradative enzymes. Genes activated by injury can be bad
ones, initiating a vicious cycle of enzyme degradation that
causes fibrillation on the cartilage surface while chewing up
studies involving cow tissues show that injured cartilage
appears to generate increased levels of HDAC enzymes, raising
the specter that they play a key role in activating the
changes leading to cartilage damage. But a pharmaceutical
agent that inhibits HDAC, already being tested as a treatment
for lymphoma, slows down the degradation of cartilage, the
Pitt team has found.
it holds promise as a treatment, with the advantage of already
being tested for safety in human clinical trials as a lymphoma
treatment. It would take five or more years before any
treatment is available, if all goes well with the research.
we know the effects, we can stop them with treatment,"
said Ulici, a key figure in the series of studies. "If we
can do that, we can prevent osteoarthritis and its changes in
the pharmaceutical agent doesnít stop cartilage degradation,
"we do see good improvement," Ulici said. "The
inflammatory molecules are going down."
the goal is to prevent degradation from happening in the first
place," Tuan said. "Based on Veronicaís findings,
if someone gets banged up one way or another, thereís a way
to make sure HDAC activity is involved, then use inhibitors
that are injected to avoid degradation" of the cartilage.
even more news that could advance treatments for
team also is using tissue engineering to develop human tissue
and cartilage in a laboratory dish that can be used to test
the effect of drugs. The live model of human joint tissue is
being heralded as the creation of "the first example of
living human cartilage grown on a laboratory chip."
the engineered cartilage tissue on a computer chip will serve
"as a test-bed for researchers to learn about how
osteoarthritis develops" and to develop new drugs.
hope that the methods weíre developing will really make a
difference, both in the study of the disease and, ultimately,
in treatments for people with cartilage degeneration or joint
injuries," said Mr. Tuan, who also serves as director of
the McGowan Institute for Regenerative Medicine and director
of the Center for Military Medicine Research at the Pitt
School of Medicine.
the Arthritis Foundation website states, "leads to
632,000 joint replacements per year, with a total cost of $128
billion in 2012 for medical care and indirect expenses,
including lost wages and productivity. One in two people will
develop a form of arthritis in their lifetime."
distinct from rheumatoid arthritis, an autoimmune disease that
causes chronic inflammation in flexible joints, with potential
to lead to severe disability if left untreated. But it affects
less than 1 percent of Americans.
foundation said trends suggest that "half of all adults
will develop symptomatic osteoarthritis of the knee at some
point in their lives and the risk increases with obesity to
two of every three obese adults."
older than 50 are more commonly affected by osteoarthritis
than men, with it typically beginning after age 40.
arthritis is a tough opponent. Ms. Thomas, as board member of
the foundationís regional chapter, says people must work to
stave off immobility by walking and exercising. Sheís trying
to avoid another round of foot surgery. Thatís why the Pitt
research is stirring optimism for her and the Arthritis
cartilage with extra good stuff would be fantastic," she
said. "Oh, Lord, itís exciting. I canít wait."
Foundation website: www.arthritis.org.