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The Role of Panx3 in Age-Associated and Injury-Induced Intervertebral Disc Degeneration

Pannexin 3 (Panx3) is a mechanosensitive, channel-forming glycoprotein implicated in the progression of post-traumatic osteoarthritis. Despite evidence for expression in the intervertebral disc (IVD), its function in this cartilaginous joint structure remained unknown. Using knockout mice, this stud...

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Published in:International journal of molecular sciences 2021-01, Vol.22 (3), p.1080
Main Authors: Serjeant, Meaghan, Moon, Paxton M, Quinonez, Diana, Penuela, Silvia, Beier, Frank, SĂ©guin, Cheryle A
Format: Article
Language:English
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Summary:Pannexin 3 (Panx3) is a mechanosensitive, channel-forming glycoprotein implicated in the progression of post-traumatic osteoarthritis. Despite evidence for expression in the intervertebral disc (IVD), its function in this cartilaginous joint structure remained unknown. Using 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 was associated with decreased gene expression of , , and 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 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 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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22031080