Cytokinins Are Age- and Injury-Responsive Molecules That Regulate Skeletal Myogenesis

Area of Science:

• Muscle Biology
• Plant Signaling Molecules
• Regenerative Medicine

Background:

• Myogenesis is crucial for muscle development and repair.
• Cytokinins (CTKs), plant-derived signaling molecules, were found in cultured muscle cells.
• Isopentenyladenine (iP) was the most abundant CTK in muscle cultures.

Purpose of the Study:

• To investigate the presence of CTKs in regenerating muscle tissue in vivo.
• To characterize the effects of iP and isopentenyladenosine (iPR) on muscle cell proliferation and differentiation.
• To compare CTK effects with adenine, adenosine, kinetin, and kinetin riboside.

Main Methods:

• Induced muscle injury and repair in mice using cardiotoxin.
• Collected gastrocnemius muscle samples at 3 and 7 days post-injury.
• Analyzed CTK presence using ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-(ESI+)-HRMS/MS).

Main Results:

• Four CTKs (N6-benzyladenine, dihydrozeatin-9-N-glucoside, iPR, and 2-methylthio-isopentenyladenosine) were detected in regenerating muscle.
• 2-methylthio-isopentenyladenosine levels were influenced by aging and injury, increasing only in younger mice.
• iPR and kinetin riboside reduced myoblast proliferation and impaired myotube formation, while iP increased proliferation biphasically.

Conclusions:

• CTKs are present in muscle tissue and are responsive to injury and aging.
• The biological activity of CTKs in muscle cells is modulated by structural features like riboside conjugation and side chain.
• Findings offer insights into CTK roles in muscle metabolism and differentiation, suggesting potential therapeutic applications in regenerative medicine.