Fluorescent Dye Reveals Biochemical Conversations Between Cartilage and Bone in Early Osteoarthritis

Image: Alizarin complexone via the intra-articular injection can enter different directions in the joint (Photo courtesy of FASEB BioAdvances; doi.org/10.1096/fba.2024-00103)

Osteoarthritis (OA) is a painful condition where the cartilage in a joint deteriorates, causing bone-on-bone contact. This articular cartilage also calcifies, turning into bone. The progressive condition is prevalent in individuals over 60, as well as those with certain metabolic disorders or who experience repetitive joint stress. Although there is no cure, early interventions may help slow further damage. However, detecting OA in its early stages, before the onset of pain, has been challenging. Now, researchers have discovered that a fluorescent dye might allow them to "listen" to biochemical interactions between cartilage and bone during the earliest stages of OA—even before pain begins. This unexpected discovery, made through research on mice, could pave the way for new treatments.

Researchers at Sidney Kimmel Medical College of Thomas Jefferson University (Philadelphia, PA, USA) investigated whether articular cartilage becomes calcified in the early stages of OA. They used a mouse model in which the right knee displays symptoms resembling those of human OA. The team injected a fluorescent red dye called alizarin complexone, which binds to calcium-containing crystals, into both knees. Surprisingly, they found no fluorescence on the surface of the articular cartilage, where they had expected to see early calcification. Instead, the dye stained the tidemark region, a boundary between the articular cartilage and the layer of calcified cartilage on the bone. The researchers also observed that the osteoarthritic mice had more alizarin dye in the calcified cartilage and subchondral bone compared to the controls. This increased dye diffusion suggests that the knee joint in early OA is more permeable than in normal joints.

When injected, the dye first enters the synovial fluid, which lubricates the joints. In additional experiments, the team found that the dye moved throughout the joint via three expected pathways. However, they also discovered a new pathway, through the tidemark, into the blood vessels in the outer bone layer, known as the periosteum. The fluorescence signal was stronger in the periosteum and subchondral bone of OA-affected joints compared to controls. These findings, published in FASEB BioAdvances, reveal that alizarin complexone can detect diffusion, or biochemical communication, between the articular cartilage, calcified cartilage, and subchondral bone. This diffusion is heightened in the early stages of OA. With this new tool, researchers can further explore OA progression, potentially leading to the development of novel treatments.