Molecular Advances in Intra-Articular Injections for Knee Osteoarthritis

Knee osteoarthritis (KOA) is a common musculoskeletal condition characterized by progressive cartilage loss, subchondral bone alterations, and persistent, low-grade synovial inflammation. There is growing evidence indicates that KOA should be viewed not only as a degenerative disorder but also as a multifaceted inflammatory process driven by complex interactions among immune cells, cytokines, and cartilage-related molecular pathways. This review outlines recent molecular advances related to intra-articular injection therapies and their proposed mechanisms of action. Corticosteroid (CS) injections provide short-term pain relief by suppressing inflammatory activity; however, repeated administration raises concerns about cartilage integrity. Hyaluronic acid (HA) injections improve joint lubrication and restore viscoelasticity and modulate inflammatory signals, particularly in the early stages of the disease. Platelet-rich plasma (PRP) has gained attention as a biologically active therapy that modulates inflammatory cascades and support tissue repair by releasing diverse growth factors. Combined administration of PRP and HA may produce complementary biological effects; however, current clinical evidence is inconclusive. Regenerative modalities, such as fat-derived orthobiologics (FDO) and mesenchymal stem cell (MSC) therapies, show promise due to their paracrine actions on macrophage behavior and extracellular matrix regulation. Emerging evidence supports the investigation of exosomes, hyperosmolar dextrose, and botulinum toxin as novel intra-articular therapies, with exosomes representing a promising cell-free regenerative approach. Overall, intra-articular interventions play an important role in KOA management, though further studies are required to determine their long-term structural impact.