It is now established that Osteoarthritis is inflammatory. Inflammation in the synovium manifests as joint effusion, while inflammation in the cartilage and subchondral bone can "silently" progress to chondrolysis, bone marrow oedema and new bone formation (osteophytes) we know as degenerative OA.
While the Osteoclast is the key player in bone inflammation, the Macrophage is the main perpetrator in synovial inflammation.
Now that we know that macrophages are the main perpetrators of synovial inflammation in OA resulting in recurrent joint effusion, therapy can be targeted more effectively against them.
This study found that a conjugate of Methotrexate and Hyaluronic Acid (HA) injected into the swollen OA joint worked, while injecting either separately or an unconjugated mixture did not.
This makes sense to me. Macrophages are scavenger cells, gobbling up bits of bugs and cell debris to present them to "professional" immune cells for surveillance of any possible threat. By conjugating the MTX with HA, the latter acts as the trojan horse to sneak concentrated doses of the MTX to knock out the macrophages without causing collateral damage or systemic spillage.
This is smart re-engineering of "old" medicines to deliver precision medicine👍