Nearly 1 in 4 adults in the United States suffers from arthritis, and a much bigger proportion is burdened by joint pain and inflammation. The primary cause is the loss of articular cartilage, the smooth, white tissue that covers the ends of bones where they come together to form joints, cushioning the ends of our bones and absorbing shocks. This cartilage naturally thins with age, or due to trauma and disease. Once this happens, bones can rub against each other, causing pain and inflammation, eventually leading to arthritis.
Cartilage has very limited regenerative potential, so once it’s injured or thinned out there hasn’t been much that could be done to correct the problem, short of full joint replacements (e.g., hips, knees). But those can only be done through highly invasive procedures and even then work only as temporary solutions.
Fortunately, this might change in the near future as a group Stanford researchers recently had a breakthrough in regenerating cartilage in mice. The research builds on a technique called microfracture, in which tiny holes are drilled in the surface of a joint. This causes the body to create new tissue in the joint, though it stops short of becoming cartilage.
The innovation comes in the manipulation of the process that is triggered by microfracture. Now, the skeletal stem cells in the joint are encouraged to start along the path of becoming bone, but are stopped in the process at the cartilage step. To initiate bone formation, the researchers used a molecule called bone morphogenetic protein 2 (BMP2); they then used another molecule to inhibit the signaling of a third molecule important in bone formation called vascular endothelial growth factor (VEGF).
In the words of Charles Chan, the lead researcher, by applying this start/stop technique:
“what we ended up with was cartilage that is made of the same sort of cells as natural cartilage with comparable mechanical properties, unlike the fibrocartilage that we usually get. It also restored mobility to osteoarthritic mice and significantly reduced their pain.”
As a proof of principle that this procedure might also work in humans, the researchers transferred human tissue into mice and were able to show that human skeletal stem cells could be manipulated toward bone development but then stopped at the cartilage stage as well.
What Comes Next
Chan and his team are now trying to replicate the same process in larger animals and, if successful, that would lead to starting human clinical trials. The good news is that the use of the two molecules, BMP2 and the VEGF inhibitor, have already been approved as safe and effective for use in humans by the FDA. According to Dr Michael Longaker, another member of the research team,
“one idea is to follow a ‘Jiffy Lube’ model of cartilage replenishment. You don’t wait for damage to accumulate — you go in periodically and use this technique to boost your articular cartilage before you have a problem.”
So, one day, avoiding chronic joint pain and arthritis might be as easy as changing the oil in your car!