The role of Pannexin 3 in forced exercise bone remodelling and its potential implications for osteoarthritis

Abstract

Exercise such as running has been hypothesized to be a factor of osteoarthritis development. However, the relationship is unclear as differences in genetic backgrounds may influence the risk of osteoarthritis (OA). The gene Panx3 codes for the Pannexin 3 protein (PANX3), a mechanically sensitive channel that allows for the passage of various signalling molecules in both chondrocytes and osteoblasts (Boassa et al., 2007; Penuela et al., 2013; Zhang et al., 2021). We have previously shown PANX3 to be protective in traumatic osteoarthritis, however beneficial in age-induced osteoarthritis (Moon et al., 2021), suggesting that PANX3’s role in osteoarthritis development is context specific. As such, the present study aimed to investigate the role of PANX3 in an exercise model of osteoarthritis development. To study this objective, adult male and female WT and Panx3 KO mice were subjected to a daily running protocol for 6 weeks. Knee samples of the mice were then analyzed through the Osteomeasure software. Although no cartilage defects indicating osteoarthritis was observed in any of the groups, the female KO mice had significantly more subchondral bone after forced exercise than all other groups. This data suggests that PANX3 is important in exercise induced subchondral bone remodelling. Considering changes in subchondral bone may precede cartilage degradation in OA, Panx3 KO mice may be more susceptible to non-traumatic OA development due to abnormal subchondral bone remodellin

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