Low-Intensity Pulsed Ultrasound Promotes the Repair of Achilles Tendinopathy by Downregulating the JAK/STAT Signaling Pathway in Rabbits.

Tendinopathy is a complex tendon injury or pathology outcome, potentially leading to permanent impairment. Low-intensity pulsed ultrasound (LIPUS) is emerging as a treatment modality for tendon disorders. However, the optimal treatment duration and its effect on tendons remain unclear. This study aims to investigate the efficacy of LIPUS in treating injured tendons, delineate the appropriate treatment duration, and elucidate the underlying treatment mechanisms through animal experiments. Ninety-six three-month-old New Zealand white rabbits were divided into normal control (NC) and model groups. The model group received Prostaglandin E2 (PGE2) injections to induce Achilles tendinopathy. They were then divided into model control (MC) and LIPUS treatment (LT) groups. LT received LIPUS intervention with a 1 MHz frequency, a pulse repetition frequency (PRF) of 1 kHz, and spatial average temporal average sound intensity (ISATA ) of 100 mW/cm2 . MC underwent a sham ultrasound, and NC received no treatment. Assessments on 1, 4, 7, 14 and 28 days after LIPUS treatment included shear wave elastography (SWE), mechanical testing, histologic evaluation, RNA sequencing, polymerase chain reaction (PCR), and western blot (WB) analysis. SWE results showed that the shear modulus in the LT group was significantly higher than that in the MC group after LIPUS treatment for 7 days. Histological results demonstrated improved tendon tissue alignment and fibroblast distribution after LIPUS treatment. Molecular analyses suggested that LIPUS may downregulate the JAK/STAT signaling pathway and regulate inflammatory and matrix-related factors. We concluded that LIPUS treatment enhanced injured tendon elasticity and accelerated Achilles tendon healing. The study highlighted the JAK/STAT signaling pathway as a potential therapeutic target for LIPUS treatment of Achilles tendinopathy, guiding future research.