Synovial Tissue May Hold Secret to Treating Osteoarthritis in Horses

The inner lining of the joint, called the synovium, secretes proteins believed to protect cartilage from the devastating effects of inflammation induced by interleukin (IL)-1β. The synovium may therefore represent a novel source of factors, such as proteins, that could serve as disease-modifying agents capable of treating equine osteoarthritis.

“Veterinarians do not currently have any disease-modifying drugs that can stop or reverse cartilage breakdown. Instead, symptom-modifying drugs are used to help control the pain and inflammation associated with osteoarthritis. In addition, oral joint health supplements are popular among both recreational and professional riders as a method to support longevity and performance,” explained Catherine Whitehouse, M.S., Kentucky Equine Research nutrition advisor.

Researchers are therefore actively seeking disease-modifying drugs for osteoarthritis. One potential source of these substances is the synovium. Cornell University researchers are on the forefront of this research.^* “The scientists sought proteins capable of inhibiting cartilage breakdown, or catabolism, caused by IL-1β,” Whitehouse said.

In the study, the researchers incubated cartilage with IL-1β or with IL-1β and synovial cells (synoviocytes). Loss of glycosaminoglycans (GAGs) from the cartilage was used as a measure of osteoarthritis. GAGs are a major component of cartilage, essential for their shock-absorbing capability during locomotion. In addition, proteins in the cartilage medium excreted by synoviocytes—referred to as the synovium secretome—were collected and analyzed.

As expected, GAGs decreased markedly when cartilage was cultured in the presence of IL-1β. When cartilage was incubated with IL-1β and synoviocytes, GAGs were mostly retained by the cartilage cultures.

“This study showed evidence that synovium secretome has protective properties against the catabolic effects of IL-1β,” explained Whitehouse.

To determine which components of the synovium secretome exert this protective effect, proteins were isolated from the cell cultures. Of the hundreds of proteins recognized in the synovium secretome, two were ultimately identified with known functions that could contribute to protecting cartilage from IL-1β: TIMP3 and TNFRSF11B.

First, TIMP3, or metalloproteinase inhibitor 3 precursor, was increased in the synovium secretome, and its synthesis was three times higher in cartilage cultures incubated with synoviocytes and IL-1β. This protein is known to block the action of numerous enzymes that contribute to cartilage breakdown, including matrix metalloproteinases.

Second, a substantial increase in TNFRSF11B was observed when cartilage and synoviocytes were cultured with IL-1β compared to cultures without IL-1β. Further, the synthesis of TNFRSF11B was 10 times higher in cultures with IL-1β. This protein is known to suppress the programmed death of cartilage cells and play a role in maintaining cartilage health.

This work shows that the synovium secretome may produce proteins capable of protecting cartilage from IL-1β. Further, evaluation of the secretome may reveal additional proteins capable of acting as disease-modifying products for combating IL-1β-mediated cartilage catabolism.

Further, the researchers suggested that multiple components of the synovium secretome could function together to “yield a more broadly therapeutic disease-modifying osteoarthritis drug than targeting any single bioactive factor.”

While veterinarians are currently limited to symptom-modifying drugs for osteoarthritis, Whitehouse emphasized the importance of a well-rounded joint health program, which includes joint supplements containing glucosamine, chondroitin sulfate, hyaluronic acid, and omega-3 fatty acids.

“The anti-inflammatory properties of long-chain polyunsaturated omega-3 fatty acids confer many health benefits, making them versatile supplements to combat inflammation, including that within joints,” said Whitehouse.

She added, “In addition to joint supplements, make sure your horse is receiving a complete and balanced ration as the long-term effects of inadequate nutrient intake can lead to poor health and performance outcomes, including osteoarthritis.”

^*Hernandez, S.M., L. Begum, L.E. Keller, Q. Fu, S. Zhang, and L.A. Fortier. 2022. Synovium secretome as a disease-modifying treatment for equine osteoarthritis. American Journal of Veterinary Research 83(10). doi: 10.2460/ajvr.22.05.0082.