Tamoxifen promotes myogenic differentiation and skeletal muscle regeneration via activation of the GRP94

  • Biochem Biophys Res Commun. 2026 Aug 20:827:154022. doi: 10.1016/j.bbrc.2026.154022.
Lei Xing  1 ,  Kun Zhang  1 ,  Yi Han  1 ,  Huaixin Teng  1 ,  Yuxi Wang  1 ,  Shuang Li  2
Affiliations
  • 1. Key Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, Northeast Agricultural University, Harbin, China; Laboratory of Cell and Developmental Biology, Northeast Agricultural University, Harbin, China.
  • 2. Key Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, Northeast Agricultural University, Harbin, China; Laboratory of Cell and Developmental Biology, Northeast Agricultural University, Harbin, China. Electronic address: [email protected].
PMID: 42208231 DOI: 10.1016/j.bbrc.2026.154022
Abstract

Efficient skeletal muscle repair remains a significant clinical challenge due to the lack of safe pharmacological interventions. Our work identifies Tamoxifen as a potent driver of muscle regeneration, operating through the GRP94. In C2C12 myoblasts, Tamoxifen treatment directly triggered myogenic differentiation and accelerated myotube formation in a dose-dependent manner, alongside the marked upregulation of MyoD, Myogenin (MyoG), and MYHC. These pro-myogenic effects were effectively abolished upon GRP94 inhibition, confirming its role as an essential mediator. In vivo, using a bupivacaine-induced injury model, we observed that 10 mg/kg Tamoxifen significantly expedited tissue repair and increased the cross-sectional area (CSA) of regenerating myofibers. Collectively, our findings demonstrate for the first time that Tamoxifen orchestrates muscle repair by modulating GRP94, offering a promising strategy for treating acute injury and chronic muscle wasting.

Keywords
GRP94; Myogenic differentiation; Regeneration; Skeletal muscle injury; Tamoxifen.
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