Denervation Atrophy of Skeletal Muscle is Not Influenced by Numb Levels in Mice

Abdurrahman Aslan, Lauren Harlow, Xin Hua Liu, Rita De Gasperi, William A. Bauman, Marco Brotto, Christopher P. Cardozo

Research output: Contribution to journalArticlepeer-review

Abstract

Skeletal muscle undergoes rapid and extensive atrophy following nerve transection though the underlying mechanisms remain incompletely understood. We previously showed transiently elevated Notch 1 signaling in denervated skeletal muscle that was abrogated by administration of nandrolone (an anabolic steroid) combined with replacement doses of testosterone. Numb is an adaptor molecule present in myogenic precursors and skeletal muscle fibers that is vital for normal tissue repair after muscle injury and for skeletal muscle contractile function. It is unclear whether the increase in Notch signaling observed in denervated muscle contributes to denervation and whether expression of Numb in myofibers slows denervation atrophy. To address these questions, the degree of denervation atrophy, Notch signaling, and Numb expression was studied over time after denervation in C57B6J mice treated with nandrolone, nandrolone plus testosterone or vehicle. Nandrolone increased Numb expression and reduced Notch signaling. Neither nandrolone alone nor nandrolone plus testosterone changed the rate of denervation atrophy. We next compared rates of denervation atrophy between mice with conditional, tamoxifen-inducible knockout of Numb in myofibers and genetically identical mice treated with vehicle. Numb cKO had no effect on denervation atrophy in this model. Taken together, the data indicate that loss of Numb in myofibers does not alter the course of denervation atrophy and that upregulation of Numb and blunting of the denervation-atrophy induced activation of Notch do not change the course of denervation atrophy.

Original languageEnglish
Pages (from-to)376-384
Number of pages9
JournalInternational Journal of Medical Sciences
Volume20
Issue number3
DOIs
StatePublished - 2023

Keywords

  • aging
  • denervation atrophy
  • nandrolone
  • numb
  • sarcopenia
  • skeletal muscle

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