Mouse Study Shows Promise in the Potential Regrowth of Joint Cartilage

Joints_Compressed

According to a study published in Nature Medicine on August 17, researchers from the Stanford University School of Medicine have discovered a way to regenerate the cushion of cartilage found in joints. They demonstrated their findings in mice, which showed signs of arthritis.

The loss of articular cartilage is responsible for the joint pain that many people experience when they live with arthritis. Approximately one in four Americans lives with arthritis, and more cope with joint pain and inflammation on a regular basis.

Over time, researchers assumed that adult cartilage did not regenerate following an injury or disease because the tissue did not have skeletal stem cells that could be activated. While working with mice, however, they found that a microfracture could activate skeletal stem cells – those stem cells regenerated fibrocartilage in the joint.

This left them wondering whether they could steer the healing process toward the development of cartilage, rather than fibrocartilage. The researchers knew that as a bone develops, cells must initially go through a cartilage stage before eventually evolving – they simply wondered if they could halt the process once cells formed cartilage.

Using a molecule called bone morphogenetic protein 2 (BMP2), the researchers initiated bone formation after microfracture in mice, but blocked a signaling molecule at the midway point to prevent full bone formation.

“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,” said assistant professor of surgery Charles K.F. Chan, Ph.D. “It also restored mobility to osteoarthritic mice and significantly reduced their pain.”

To show how this method could potentially work in humans, the researchers transferred human tissue into mice that were bred not to reject the tissue. They demonstrated that the human skeletal stem cells could be directed toward bone development, halting at the cartilage development stage.

This is not the first study as of late to show promise in the realm of re-growing cartilage. A trial published at the beginning of August suggests that injections of a molecule used to store energy – adenosine triphosphate – may provoke the growth of human tissue in the body.

Researchers injected adenosine into the joints of mice whose limbs had been damaged by inflammation. They received eight weekly injections, which prompted regrowth rates of cartilage between 35% and 50%.

“Our latest study shows that replenishing adenosine stores by injection works well as a treatment for osteoarthritis in animal models of the disease, and with no apparent side effects,” said lead study author Carmen Corciulo, Ph.D., a postdoctoral fellow at NYU Langone.

However, Corciulo acknowledges that it is too soon to utilize this experimental model in humans. Clinical trials must wait for a test drug that can be safely stored for days – if not weeks – in experiments involving larger mammals.

The researchers did find that a cell-signaling pathway – transforming growth factor beta (TGF-beta) – was highly active in cartilage tissue undergoing repair after receiving adenosine. Further testing exhibited varying chemical profiles of TGF-beta signaling during breakdown, compared to growth. This is the first evidence to show that the pathway can switch function when exposed to adenosine.

The NYU Grossman School of Medicine, along with two researchers from the study, have a patent application pending for the use of adenosine and other agents that could potentially help with its binding to A2A receptor agonists, specifically for the treatment of osteoarthritis.

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