Intra-articular lubricin injections could prevent osteoarthritis following ACL injury

Injection of intra-articular lubricin following an ACL injury may reduce cartilage degeneration and the development of post-traumatic osteoarthritis, according to researchers from Rhode Island Hospital.

Knowing that ACL injury is a significant risk factor for the development of post-traumatic osteoarthritis (OA) due to the degeneration of fluids in the joint and cartilage and joint instability, Gregory Jay, MD, PhD, and colleagues from Providence, R.I., aimed to determine an effective way to counter that process, according to a press release.

“In the peri-injury period following joint trauma, joint surfaces are vulnerable to enhanced wear. This study is pointing us in the right direction, and has shown that this can potentially be mitigated by simply reintroducing the joint’s natural lubricant,” Jay stated in the press release, “We are confident that further studies will perfect the technology and this will be the way that joints will be treated in the future to prevent OA.”

Making up for lost fluid

Jay and colleagues used animal models with torn ACLs to test intra-articular injections of lubricin derived from human synoviocytes in culture, recombinant human PRG-4 (rhPRG-4), and human synovial fluid — three types of fluid that could substitute for the loss of synovial fluids in a traumatized joint, according to the release.

The researchers found that cartilage deterioration can be limited, which is evident by using a widely accepted OA biomarker that shows the slowing of cartilage type II collagen breakdown. Human synoviocyte lubricin was the most effective at slowing cartilage degeneration, although treatment with rhPRG-4 could also be considered successful.

The injection of lubricin into a traumatized joint encourages the joint to produce its own lubricin, according to the researchers. “We found that you are limiting deterioration of the joint endogenously by the greater secretion of the lubricin molecule. Basically, by placing the lubricin there, it encouraged the joint’s normal activity to produce this molecule,” Jay stated in the release.

‘Tribosupplementation’

Jay noted that the findings represent a major advance in the existing technology of viscosupplementation injections. “We now know that joint lubrication has little to do with viscosity. We are inventing a new type of joint lubrication strategy: tribosupplementation, taken from the Greek, meaning to wear or to rub,” he said.

Lubricin is a promising biologic candidate to prevent OA following an ACL injury, Jay noted in the release. The creation of new therapeutic biologics is important because their specificity and low toxicity profiles make them safer for patients, with fewer complications.

With their study, Jay and colleagues concluded that a reduction in cartilage damage was seen following treatment with any of the three types of lubricin they evaluated, and that intra-articular lubricin injection following ACL injury may be beneficial in minimizing cartilage degeneration and slowing the development of posttraumatic OA.

Reference:
Jay GD, Fleming BC, Watkins BA, et al. Prevention of cartilage degeneration and restoration of chondroprotection by lubricin tribosupplementation in the rat following anterior cruciate ligament transection. Arthritis Rheum. 2010;62(8):2382-2391. doi:10.1002/art.27550.