Modulation of Deiodinase Types 2 and 3 during Skeletal Muscle Regeneration

Abstract

The muscle stem-cell niche comprises numerous cell types, which coordinate the regeneration process after injury. Thyroid hormones are one of the main factors that regulate genes linked to skeletal muscle. In this way, deiodinase types 2 and 3 are responsible for the fine-tuning regulation of the local T3 amount. Although their expression and activity have already been identified during muscle regeneration, it is of utmost importance to identify the cell type and temporal pattern of expression after injury to thoroughly comprehend their therapeutic potential. Here, we confirmed the expression of Dio2 and Dio3 in the whole tibialis anterior muscle. We identified, on a single-cell basis, that Dio2 is present in paired box 7 (PAX7)-positive cells starting from day 5 after injury. Dio2 is present in platelet derived growth factor subunit A (PDGFA)-expressing fibro-adipogenic progenitor cells between days 7 and 14 after injury. Dio3 is detected in myogenic differentiation (MYOD)-positive stem cells and in macrophages immediately post injury and thereafter. Interestingly, Dio2 and Dio3 RNA do not appear to be present in the same type of cell throughout the process. These results provide further insight into previously unseen aspects of the crosstalk and synchronized regulation of T3 in injured muscle mediated by deiodinases. The set of findings described here further define the role of deiodinases in muscle repair, shedding light on potential new forms of treatment for sarcopenia and other muscular diseases.