Tuesday, May 21, 2013

New stem cell culprit in osteoarthritis points to potential therapy

Image by Leonard John Matthews
For those of us with painful stiff knees caused by osteoarthritis a new theory on what causes it doesn’t excite us much if the news is followed by the usual retort in this field: but there is nothing we can do about it. This time, a group at John’s Hopkins has discovered a potential new contributor to the destruction of our cushioning cartilage and also discovered a possible way to stop the culprit. If knees could smile...

The prevailing theories suggest that any number of physical traumas can eat away at the cartilage. The Hopkins team found evidence in mice that the physical trauma also results in parts of the neighboring bone being chewed away. When your body detects that bone destruction you secrete a protein that summons your own stem cells to repair the damage. But the stem cells over do it, producing more bone than is needed and putting further pressure on the cartilage eroding it even more.

The researchers found that if they injected an antibody to that protein in the joints, they could halt this over production of new bone and slow the damage to the cartilage. So the repair was not just about replacing the cushion of cartilage. A press release from the university quotes the lead researcher Xu Cao:
“If there is something wrong with the leg of your chair and you try to fix it by replacing the cushion, you haven’t solved the problem.”
This work needs to be replicated in people, but the team did detect evidence in a computer simulation of the human knee that the same scenario may be at play.

There has long been speculation that osteo is not just a mechanical issue. There has been some evidence of the body’s natural feedback system, potentially the immune system, is also playing a role. CIRM grantee William Robinson discussed this possibility in a Spotlight on disease presentation in this video.

His colleague at Stanford, Mark Genovese, offered a good overview of arthritis at the same meeting. He noted that arthritis is an imbalance between joint destruction and tissue remodeling for repair.

The current paper provides a good reminder of the ability of stem cells to generate multiple kinds of tissues. The stem cells that overproduced bone for the Hopkins team probably came from mesenchymal stem cells, a class of stem cell that can become, bone, cartilage, muscle or fat. The trick for arthritic knees is to coax them into becoming new cartilage, not bone. We now have one more piece of the recipe for that goal.

There's more about stem cell approaches to treated osteoarthritis on our website, including this Story of Hope about a patient with the disease and a list of awards we're funding to address the condition.

D.G.

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