NTN1 and osteoarthritis: Netrin-1 is an axon guidance protein secreted by osteoclasts.54 It promotes the innervation of sensory nerves during subchondral bone remodeling in TMJ-OA.9 Regional increase in PGE2 levels within the remodeled subchondral bone also activates sensory nerve endings, augmenting pain levels.19 Nevertheless, blocking netrin-1 and PGE2 only partially relieves osteoarthritis pain.