Sex‐dependent role of Pannexin 1 in regulating skeletal muscle and satellite cell function

Freeman, Emily; Langlois, Stéphanie; Scott, Kaylee; Ravel‐Chapuis, Aymeric; Jasmin, Bernard J.; Cowan, Kyle N.

doi:10.1002/jcp.30850

Cited by 3 publications

(13 citation statements)

References 51 publications

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“…Interestingly, although Panx1 KO mice show an increased number of regenerated fibers after acute injury, these newly formed fibers are smaller in male mice. 123 These findings indicate that Panx1 plays a crucial role in regulating muscle development, regeneration, and the number of satellite cells in mice, with notable sex differences.…”

Section: Panxs In Musculoskeletal Systemmentioning

confidence: 92%

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Pannexins in the musculoskeletal system: new targets for development and disease progression

Luo,

Zheng,

Xiao

et al. 2024

Bone Res

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During cell differentiation, growth, and development, cells can respond to extracellular stimuli through communication channels. Pannexin (Panx) family and connexin (Cx) family are two important types of channel-forming proteins. Panx family contains three members (Panx1-3) and is expressed widely in bone, cartilage and muscle. Although there is no sequence homology between Panx family and Cx family, they exhibit similar configurations and functions. Similar to Cxs, the key roles of Panxs in the maintenance of physiological functions of the musculoskeletal system and disease progression were gradually revealed later. Here, we seek to elucidate the structure of Panxs and their roles in regulating processes such as osteogenesis, chondrogenesis, and muscle growth. We also focus on the comparison between Cx and Panx. As a new key target, Panxs expression imbalance and dysfunction in muscle and the therapeutic potentials of Panxs in joint diseases are also discussed.

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Section: Panxs In Musculoskeletal Systemmentioning

confidence: 92%

“…Recently, a unique sex-dependent function of Panx1 has been discovered in skeletal muscle. 123 In global Panx1 KO male mice, muscle fiber size and strength, as well as the number of satellite cells (SCs), are reduced. Additionally, early SC differentiation and myoblast fusion are also altered in these male mice.…”

Section: Panxs In Musculoskeletal Systemmentioning

confidence: 99%

Pannexins in the musculoskeletal system: new targets for development and disease progression

Luo,

Zheng,

Xiao

et al. 2024

Bone Res

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“…Pannexin 1 (Panx1 in rodents; PANX1 in humans) forms single membrane channels permeable to molecules > 1 kDa in size such as ATP [33]. We have previously shown that pannexin 1 plays a key role in myogenesis in humans and mice [19,28]. In addition to differentiated skeletal muscle fibers, PANX1/Panx1 is expressed in SCs and myoblasts [19,36,42].…”

Section: Introductionmentioning

confidence: 99%

“…We have previously shown that pannexin 1 plays a key role in myogenesis in humans and mice [19,28]. In addition to differentiated skeletal muscle fibers, PANX1/Panx1 is expressed in SCs and myoblasts [19,36,42]. PANX1/Panx1 levels increase during myogenesis in vitro, as well as in muscle development and regeneration in vivo [28,36].…”

Section: Introductionmentioning

confidence: 99%

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Pannexin 1 dysregulation in Duchenne muscular dystrophy and its exacerbation of dystrophic features in mdx mice

Freeman,

Langlois,

Leyba

et al. 2024

Skeletal Muscle

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Background Duchenne muscular dystrophy (DMD) is associated with impaired muscle regeneration, progressive muscle weakness, damage, and wasting. While the cause of DMD is an X-linked loss of function mutation in the gene encoding dystrophin, the exact mechanisms that perpetuate the disease progression are unknown. Our laboratory has demonstrated that pannexin 1 (Panx1 in rodents; PANX1 in humans) is critical for the development, strength, and regeneration of male skeletal muscle. In normal skeletal muscle, Panx1 is part of a multiprotein complex with dystrophin. We and others have previously shown that Panx1 levels and channel activity are dysregulated in various mouse models of DMD. Methods We utilized myoblast cell lines derived from DMD patients to assess PANX1 expression and function. To investigate how Panx1 dysregulation contributes to DMD, we generated a dystrophic (mdx) mouse model that lacks Panx1 (Panx1−/−/mdx). In depth characterization of this model included histological analysis, as well as locomotor, and physiological tests such as muscle force and grip strength assessments. Results Here, we demonstrate that PANX1 levels and channel function are reduced in patient-derived DMD myoblast cell lines. Panx1−/−/mdx mice have a significantly reduced lifespan, and decreased body weight due to lean mass loss. Their tibialis anterior were more affected than their soleus muscles and displayed reduced mass, myofiber loss, increased centrally nucleated myofibers, and a lower number of muscle stem cells compared to that of Panx1+/+/mdx mice. These detrimental effects were associated with muscle and locomotor functional impairments. In vitro, PANX1 overexpression in patient-derived DMD myoblasts improved their differentiation and fusion. Conclusions Collectively, our findings suggest that PANX1/Panx1 dysregulation in DMD exacerbates several aspects of the disease. Moreover, our results suggest a potential therapeutic benefit to increasing PANX1 levels in dystrophic muscles.

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Pannexin1 deletion in lymphatic endothelium affects lymphatic function in a sex‐dependent manner

Ehrlich,

Pelli,

Pick

et al. 2024

Physiological Reports

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The lymphatic network of capillaries and collecting vessels ensures tissue fluid homeostasis, absorption of dietary fats and trafficking of immune cells. Pannexin1 (Panx1) channels allow for the passage of ions and small metabolites between the cytosol and extracellular environment. Panx1 channels regulate the pathophysiological function of several tissues in a sex‐dependent manner. Here, we studied the role of Panx1 in lymphatic function, and potential sex‐dependent differences therein, in Prox1‐CreERT2Panx1fl/fl and Panx1fl/fl control mice. Panx1 expression was higher in lymphatic endothelial cells (LECs) of male mice. Lymphatic vessel morphology was not affected in Prox1‐CreERT2Panx1fl/fl male and female mice. Lymphatic drainage was decreased by 25% in male Prox1‐CreERT2Panx1fl/fl mice, but was similar in females of both genotypes. Accordingly, only male Prox1‐CreERT2Panx1fl/fl mice exhibited tail swelling, pointing to interstitial fluid accumulation in males upon Panx1 deletion in LECs. Moreover, serum triglyceride and free fatty acid levels raised less in Prox1‐CreERT2Panx1fl/fl mice of both sexes in an oral lipid tolerance test. Finally, the percentage of migratory dendritic cells arriving in draining lymph nodes was increased in Prox1‐CreERT2Panx1fl/fl female mice, but was comparable between male mice of both genotypes. Our results point to a LEC‐specific role for Panx1 in the functions of the lymphatic system.

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Sex‐dependent role of Pannexin 1 in regulating skeletal muscle and satellite cell function

Cited by 3 publications

References 51 publications

Pannexins in the musculoskeletal system: new targets for development and disease progression

Pannexins in the musculoskeletal system: new targets for development and disease progression

Pannexin 1 dysregulation in Duchenne muscular dystrophy and its exacerbation of dystrophic features in mdx mice

Pannexin1 deletion in lymphatic endothelium affects lymphatic function in a sex‐dependent manner

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