Abstract
Pannexin 3 (Panx3) is a mechanosensitive, channel-forming glycoprotein implicated in the progression of post-traumatic osteoarthritis. Despite evidence for Panx3 expression in the intervertebral disc (IVD), its function in this cartilaginous joint structure remained unknown. Using Panx3 knockout mice, this study investigated the role of Panx3 in age-associated IVD degeneration and degeneration induced by annulus fibrosus (AF) needle puncture. Loss of Panx3 did not significantly impact the progression of age-associated histopathological IVD degeneration; however, loss of Panx3 was associated with decreased gene expression of Acan, Col1a1, Mmp13 and Runx2 and altered localization of COLX in the IVD at 19 months-of-age. Following IVD injury in the caudal spine, histological analysis of wild-type mice revealed clusters of hypertrophic cells in the AF associated with increased pericellular proteoglycan accumulation, disruptions in lamellar organization and increased lamellar thickness. In Panx3 knockout mice, hypertrophic AF cells were rarely detected and AF structure was largely preserved post-injury. Interestingly, uninjured IVDs adjacent to the site of injury more frequently showed evidence of early nucleus pulposus degeneration in Panx3 knockout mice but remained healthy in wild-type mice. These findings suggest a role for Panx3 in mediating the adaptive cellular responses to altered mechanical stress in the IVD, which may buffer aberrant loads transferred to adjacent motion segments.
Highlights
As a leading cause of disability, back pain poses a significant socioeconomic burden that is only predicted to rise as the population ages [1,2,3]
Using a percutaneous intervertebral disc (IVD) puncture model in the caudal spine (Figure 5A), we investigated the role of Pannexin 3 (Panx3) in injury-induced IVD degeneration to assess its role in the trophic cells did not consistently show expression of markers of chondrocyte hypertrophy (Figure 4B), suggesting a phenotype distinct from that of hypertrophic chondrocytes
Given the catabolic role of Panx3 in related tissues, we investigated the role of Panx3 in the IVD using previously characterized Panx3-/- mice [19]
Summary
As a leading cause of disability, back pain poses a significant socioeconomic burden that is only predicted to rise as the population ages [1,2,3]. While the causes of back pain are complex, several large-scale, cross-sectional studies have demonstrated a strong association between back pain and degeneration of the intervertebral discs (IVDs) [4,5,6]. Despite efforts to improve the management of back pain associated with IVD degeneration, no diseasemodifying treatments currently exist. It functions to absorb axial loads and provide mobility to the spine. The IVD is a heterogeneous structure made up of three tissues: the central gelatinous nucleus pulposus (NP) contained by the concentric lamellar structure of the annulus fibrosus (AF), interposed between the cartilaginous endplates (CEPs) that anchor the IVDs to adjacent vertebrae. IVD function relies on the synergistic roles of its composite tissues. The radial forces exerted by the NP are balanced by tensile loads generated across the collagen bundles of the AF lamellar network [7,8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
