Salk discovery could help reverse osteoarthritis

Osteoarthritis is a common age-related condition that affects about 30 million Americans and millions more around the world. The debilitating joint pain from this condition has a significant effect on the quality of life and ability to live independently for older individuals. Scientists at the Salk Institute for Biological Sciences in California have discovered a treatment that could potentially reverse osteoarthritis. The results of their study were published in Protein and Cell, a peer-reviewed journal. In people with osteoarthritis, the cartilage between bones in a joint thins out. This leads to bone-on-bone contact which causes pain. With age, it becomes more difficult for the body to repair damaged cartilage. “Cartilage acts as a cushion between two bones,” says co-first author of the study, Paloma Martinez-Redondo. “So, when we have to move any joint, in this case the knee, we need to have a cushion there that would prevent the erosion between the two bones,” she adds. Martinez-Redondo and her colleague studied two proteins – TGF beta receptor 2 and alpha-KLOTHO – that are naturally present in the body and known to be associated with aging and cartilage production. The researchers tested the two proteins together in rats as well as human cartilage cells. “We have previous studies showing these two proteins could help us … not only to prevent the pathology but also to improve the repair,” Martinez-Redondo said. “But it was also lucky, because we tried putting them together and they worked better together.” In rats, the proteins were able to reverse osteoarthritis with cartilage growth. The protein combination also stopped the disease from returning.

On the left is a cross-section of a knee from a rat with osteoarthritis that was treated using Salk scientists’ protein therapy. On the right is a knee from a rat with osteoarthritis that was not treated. The red shows the amount of cartilage between the bones, February 4, 2020.

“From the very first time we tested this drug combination on just a few animals, we saw a huge improvement,” said Isabel Guillen-Guillen, Salk scientist and co-first author. “We kept checking more animals and seeing the same encouraging results.” The effect on human cartilage cells is also encouraging. “That’s not the same as showing how these drugs affect the knee joint in humans, but we think it’s a good sign that this could potentially work for patients,” says Martinez-Redondo. At present, therapies available to osteoarthritis patients either offer symptomatic relief of pain without addressing the underlying cause or are intrusive, such as joint replacement surgery. Human clinical trials are planned to study the efficacy and safety of this therapy that offers a more natural way to reverse osteoarthritis.