Letrozole alters transcriptomic profiles in infrapatellar fat pad from female mice: Possible involvement of aromatase inhibitor-induced arthralgias

Letrozole, is an aromatase inhibitors (AIs) preventing estrogen synthesis from testosterone, and it induces many side effects, known as the aromatase inhibitor-associated musculoskeletal syndrome (AIMSS), including arthralgias. The infrapatellar fat pad (IFP), rectus femoris and tendon are critical structural and functional components of the knee musculoskeletal system. The IFP is metabolically active and acts as a key regulator of joint inflammation and homeostasis. Meanwhile, rectus femoris and tendon tissues are highly susceptible to estrogen fluctuation and inflammatory insult, making them pivotal peripheral targets closely linked to the onset and progression of AIMSS. However, how letrozole intervention induces pathological and molecular alterations in these three key tissues remains unclear. Given the above research gaps,We integrated transcriptomic profiling to characterize molecular signatures underlying letrozole-related musculoskeletal injury. This work aims to uncover the potential aetiological mechanisms of AIMSS and identify novel molecular biomarkers and therapeutic targets for the early prevention and clinical intervention of AIMSS.