Fig. 6

Skeletal interoception in OA and its pain. In advanced OA, there is a progressive deterioration of articular cartilage, along with the development of subchondral bone sclerosis, osteophyte, bone cysts, and synovial inflammation. Elevated PGE2 in subchondral bone transmits interoceptive signals to the brain, which downregulated SNS activity to promote subchondral bone formation and sclerosis. PGE2 also activates OCs to release netrin1, which promotes sensory nerve innervation in the subchondral bone. In the chronic inflammatory phase of OA synovium, PGE2 level is elevated accompanied by decreased sympathetic nerve innervation. This suggests that the skeletal interoception circuit may be involved. The PGE2 in ST can also be released into synovial fluid promoting cartilage destruction. PGE2 prostaglandin E2, SNS sympathetic nervous system, OC osteoclast, ST synovial tissue, NE norepinephrine