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Degree

Master of Science

Program

Physiology and Pharmacology

Collaborative Specialization

Musculoskeletal Health Research

Supervisor

Séguin, Cheryle

2nd Supervisor

Beier, Frank

Co-Supervisor

Abstract

Pannexin 3 (Panx3) is a mechanosensitive, channel-forming glycoprotein implicated in the progression of post-traumatic osteoarthritis. Despite evidence for Panx3 expression in intervertebral discs (IVDs), its function here remained unknown. Using Panx3-/- mice, this study investigated the role of Panx3 in age-associated and injury-induced models of IVD degeneration. While loss of Panx3 did not significantly impact the progression of age-associated IVD degeneration, it was associated with a protective phenotype in an injury model of IVD degeneration, specifically in the annulus fibrosus (AF). Following IVD injury, WT mice showed an accumulation of enlarged cells that appeared to contribute to disrupted AF structure. In Panx3-/- IVDs, enlarged cells were rarely detected and AF structure was retained post-injury. Interestingly, uninjured IVDs adjacent to the site of injury were disrupted in Panx3-/- mice but remained healthy in WT mice. These studies suggest a role for Panx3 in mediating adaptive AF cellular responses to acute mechanical stress.

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