AMPK Signaling Pathway Regulates Tendon Regeneration via Fatty Acid Metabolism

Abstract

Tendon and ligament injuries are the most common musculoskeletal injuries, and their regeneration is a complex process due to the poor natural healing ability of these tissues. The current therapies for tendon repair are limited in efficacy and their cellular and molecular mechanisms remain unclear. In this study, we identified AMP-activated protein kinase (AMPK) as a markedly upregulated factor in newborn tendons with high regenerative capacity. Both in vivo and in vitro experiments demonstrated that treatment with dorsomorphin, an AMPK inhibitor, significantly decreased the tendon healing potential. Further analyses revealed that carnitine palmitoyltransferase 1A, a key enzyme, is a putative downstream target of AMPK and is closely associated with the proliferation and tenogenic differentiation of tendon stem/progenitor cells. Collectively, we highlight the essential role of AMPK in tendon repair and propose a potential therapeutic intervention for tendon injuries.