26 Scientific American, June 2022 Illustration by Fatinha Ramos
THE SCIENCE
OF HEALTH
Claudia Wallis is an award-winning science journalist
whose work has appeared in the New York Times, Time, Fortune
and the New Republic. She was science editor at Time and
managing editor of Scientific American Mind.“Cartilage doesn’t heal.” That’s what doctors often tell us when
we injure the flexible tissue that lines our hips, knees and shoul-
ders or when osteoarthritis has eroded it so that our joints hurt
when we move. I’ve certainly heard it myself from orthopedic
surgeons who explain that cartilage has no blood supply to bring
repair cells and nutrients to an injury site. Yet it’s always struck
me as improbable that a living tissue could not replace damaged
cells. As it turns out, recent research suggests that articular car-
tilage—the type in our joints—does have some limited repair
capacity. New insights into this ability are raising hopes for treat-
ments that could enhance healing or protect damaged cartilage
from further deterioration.
To picture articular cartilage, envision the tough, white coat-
ing on the end of a chicken bone. Most of it is a spongy material
called extracellular matrix, a mixture of water and fibrous pro-
teins pumped out by cells called chondrocytes. “There is intrin-
sic regeneration—with new tissue being formed and old tissue
chewed up and washed away—just as there is for every tissue
with the exception of tooth enamel,” explains rheumatologist Vir-
ginia Kraus of the Duke University School of Medicine. But, she
emphasizes, the renewal process in cartilage is sluggish. And it
is true that in adults the tissue has no blood supply. Instead carti-
lage gets help from what experts call dynamic loading—putting
stress or weight on the joint, which causes nutrient-carrying syno-
vial fluid to flow in and out. “That’s why exercise is so critical to
joint health,” Kraus notes. “The way you get nutrients to carti-
lage is through movement.”
Kraus is one of a small number of scientists who studies the
slow turnover in this tissue. In a surprising discovery, she and
her team reported in 2019 that the production of proteins asso-
ciated with repair and regeneration differs by joint: It is great-
er in the ankle than in the knee and greater in the knee than the
hip. Kraus refers to this gradient as “our inner salamander,”
explaining that in salamanders and other animals that can
regenerate a lost limb, this capacity is more robust in the foot
than higher up in the leg.
Her study also showed that genetic material associated with
repair is more abundant in arthritic joints than healthy ones. Just
as a limb injury launches a repair program in a salamander, osteo-
arthritis is turning it on in humans, Kraus suspects, although
“obviously the program we have is not sufficient.” Still, the repair
process may be working in the ankle, which, she notes, is far less
prone to severe arthritis than the knee or hip.
There is other evidence that human cartilage can regenerate.
A procedure called joint distraction is being tested as a way to
promote healing in patients who have bone-on-bone knee arthri-
tis and are too young to be good candidates for total knee re -
placement. (Prosthetic knees last 15 to 20 years, after which they
must be replaced in a complex surgery.) The procedure involves
placing pins above and below the knee and using an external
device for six weeks to separate the upper and lower leg bones
by five millimeters. This opens up the joint space. Patients are
encouraged to walk, but the device reduces stress, so the knee is
bathed in nutrient-laden fluid without being overburdened.
Dutch researchers have shown that the procedure leads to a
small increase in cartilage in the joint and less pain—benefits
that last at least two years and as many as 10 in some patients.
Larger clinical trials of the technique are needed, “but it’s a fas-
cinating model,” says rheumatologist Philip Conaghan of the Uni-
versity of Leeds in England.
Conaghan investigates new drugs for arthritis, including
a growth factor called sprifermin that appears to slow the loss
of cartilage in some patients. He is also looking at canakinumab,
an inflammation inhibitor that was tested as a cardiovascular
drug and showed a surprising side effect: dramatically fewer joint
replacements in recipients than in a placebo group. But Conaghan
warns that the quest for drugs that can thicken cartilage is a
tough one because of the slow and uncertain nature of repair:
“The change is so small, and it’s hard to pick it up, even with the
best imaging.”
For now, strength-building exercise remains the best strategy
for those of us with fraying joints. Conaghan recommends walk-
ing in a swimming pool. “Strong quads reduce knee pain a lot, no
matter what you’ve got going on,” he says. “All of life is about
strong muscles.”Regenerating
Damaged Joints
New research on arthritis and cartilage
opens up growing possibilities
By Claudia Wallis