How do small quantities of cartilage sodium channels play a significant role in osteoarthritis?

INTRODUCTION Osteoarthritis (OA) is a chronic degenerative joint disease affecting the entire joint, causing pain, stiffness and limitations in mobility and posing a significant burden on global health and the quality of life for millions worldwide.1 Despite its prevalence, treatment options remain limited, often focused on symptom management rather than addressing the underlying mechanisms driving joint degradation.2,3 OA is characterized by the loss of cartilage, prompting most efforts to develop disease-modifying treatments to concentrate on molecular events within the cartilage. In chondrocytes expressing Nav1.7, the blockade of Nav1.7 triggers increased secretion of HSP70 and midkine, which is crucial for Nav1.7 blockade-mediated regulation of chondrocyte biology, in turn impacting joint structure and pain in OA.9 The increased release of HSP70 and midkine upon Nav1.7 blockade of Nav1.7 expressing chondrocytes is possibly the tip of the iceberg. Given the regulatory roles of HSP70 and midkine in inflammation and chondrocyte proliferation, it is plausible that Nav1.7-positive chondrocytes engage in interactions with surrounding tissues, such as synovial membranes and subchondral bone, by influencing the release of these proteins into the synovial fluid. [...]future research should also delve into the cross-talk and communication pathways among sodium channels Nav1.7-expressing chondrocytes and other joint cells, including synovial fibroblasts and osteoblasts, as well as immune cells infiltrating the joints (Figure 1).