A2M for treatment of OA:

When someone is suffering from arthritis, cartilage-destroying chemicals affect their joints. Catabolic proteases (chemicals that cause cartilage to break down) result in pain and inflammation. The disease will eventually cause the cartilage to degrade completely, resulting in painful friction of bones rubbing together. In healthy joints, cartilage works as a buffer to prevent bone-on-bone contact.⁣

A2M is alpha-2-macroglobulin, a plasma protein made in the liver. It can halt the progression of osteoarthritis at the molecular level by inactivating the chemicals that cause cartilage breakdown. As the A2M captures and neutralizes the damaging chemicals, the body will work to eliminate them. The joint will then begin to recover, as the inflammation is subdued, and harmful chemicals are no longer present. A2M remaining in the joint will promote tissue growth and the joint can begin the restoration process. The repair will then lead to a pain-free joint.⁣

This linked journal article talks about the function of A2M in a knee joint, post-injury. It states that A2M is more highly concentrated in blood plasma than in healthy synovial fluid due to its molecular weight, and it protects and heals cartilage. In order to increase the concentration in the synovial fluid, the serum can be concentrated and injected into the joint, as a way to help the body along. There is not a large amount of data on this yet, but it looks promising. The study also suggests that A2M binds a range of cytokines, such as IL1β and TNFα and also enters into cells to regulate cellular responses to other growth factors and cytokines. Of note, A2M is shown to be inactivated in the presence of neutrophils and free radicals as seen in sepsis, likely due to complexing to proteinases. In other words, using a pure PRP sample, devoid of white cells seems prudent.