Pannexin 3deletion in mice results in knee osteoarthritis and intervertebral disc degeneration after forced treadmill running

Abstract

Pannexin 3 (Panx3) is a glycoprotein that forms mechanosensitive channels expressed in chondrocytes and annulus fibrosus cells of the intervertebral disc (IVD). Evidence suggests Panx3 plays contrasting roles in traumatic versus aging osteoarthritis (OA) and intervertebral disc degeneration (IDD). However, whether its deletion influences the response of joint tissue to mechanical stress is unknown. The purpose of this study was to determine if Panx3 deletion in mice causes increased knee joint OA and IDD after forced treadmill running. Male and female wildtype (WT) and Panx3 knockout (KO) mice were randomized to either a no exercise group (sedentary; SED) or daily forced treadmill running (forced exercise; FEX) from 24 to 30 weeks of age. Knee cartilage, tibial subchondral bone and IVD histopathology were evaluated by histology. Both male and female Panx3 KO mice developed larger superficial defects of the tibial cartilage after forced treadmill running compared to SED WT mice. Additionally, both male and female Panx3 KO mice developed a sclerotic secondary ossification center of the tibia with running. In the lower lumbar spine, both male and female Panx3 KO mice developed histopathological features of IDD after running compared to SED WT mice. Clinical Significance: These findings suggest that the combination of deleting Panx3 and forced treadmill running induces OA and causes histopathological changes associated with degeneration of the IVDs in mice.