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

Abstract

ABSTRACTPannexin 3 (Panx3) is a glycoprotein that forms mechanosensitive channels expressed in chondrocytes and annulus fibrosus cells of the intervertebral disc (IVD). Evidence suggestsPanx3plays 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 ifPanx3deletion in mice causes increased knee joint OA and IDD after forced treadmill running. Male and female wildtype (WT) andPanx3knockout (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 secondary ossification center and IVD histopathology were evaluated by histology. Both male and femalePanx3KO mice developed larger superficial defects of the tibial cartilage after forced treadmill running compared to SED WT mice. Additionally, both male and femalePanx3KO mice developed greater bone area of the tibial secondary ossification center with running. In the lower lumbar spine, both male and femalePanx3KO mice developed histopathological features of IDD after running compared to SED WT mice. These findings suggest that the combination of deletingPanx3and forced treadmill running induces OA and causes histopathological changes associated with degeneration of the IVDs in mice.