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Evidence suggests <jats:italic>Panx3<\/jats:italic> 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 forced use\u00a0is unknown. The purpose of this study was to determine if <jats:italic>Panx3<\/jats:italic> deletion in mice causes increased knee joint OA and IDD after forced treadmill running. Male and female wildtype (WT) and <jats:italic>Panx3<\/jats:italic> knockout (KO) mice were randomized to either a no\u2010exercise group (sedentary; SED) or daily forced treadmill running (forced exercise; FEX) from 24 to 30 weeks of age. Knee cartilage and IVD histopathology were evaluated by histology, while tibial secondary ossification centers were analyzed using microcomputed tomography (\u00b5CT). Both male and female <jats:italic>Panx3<\/jats:italic> KO mice developed larger superficial defects of the tibial cartilage after forced treadmill running compared with SED WT mice. Additionally, <jats:italic>Panx3<\/jats:italic> KO mice developed reduced bone volume, and female <jats:italic>PANX3<\/jats:italic> KO mice had lengthening of the lateral tubercle at the intercondylar eminence. In the lower lumbar spine, both male and female <jats:italic>Panx3<\/jats:italic> KO mice developed histopathological features of IDD after running compared to SED WT mice. These findings suggest that the combination of deleting <jats:italic>Panx3<\/jats:italic> and forced treadmill running induces OA and causes histopathological changes associated with the degeneration of the IVDs in mice.<\/jats:p>","DOI":"10.1002\/jor.25830","type":"journal-article","created":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T03:54:09Z","timestamp":1710820449000},"page":"1696-1709","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["<i>Pannexin 3<\/i> deletion in mice results in knee osteoarthritis and intervertebral disc degeneration after forced treadmill running"],"prefix":"10.1002","volume":"42","author":[{"given":"Brent","family":"Wakefield","sequence":"first","affiliation":[{"name":"Department of Anatomy and Cell Biology Schulich School of Medicine and Dentistry University of Western Ontario London Ontario Canada"},{"name":"Western's Bone and Joint Institute, The Dr. Sandy Kirkley Centre for 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