Radial Extracorporeal Shockwave Therapy Reduces Subchondral Osteoblast Senescence in Knee Osteoarthritis.

Abstract

Excess subchondral bone (SCB) turnover due to osteoblast senescence has been confirmed as the histological manifestation of early-stage osteoarthritis (OA). The therapeutic efficacy of radial extracorporeal shockwave therapy (rESWT) on osteoblast senescence in early-stage OA has not been fully elucidated. To evaluate the therapeutic potential of rESWT in enhancing SCB osteogenesis and mitigating osteoblast senescence in a rat model of knee OA. Controlled laboratory study. The expression of senescence biomarkers was evaluated by immunohistochemistry on tibial plateau samples from patients with knee OA (n = 3). Monosodium iodoacetate (MIA)-induced OA was established in 8-week-old male Sprague-Dawley rats, which were treated with 3 different doses of rESWT (0.096, 0.128, or 0.16 mJ/mm²; n = 6 per group) for 4 weeks. Articular cartilage and SCB samples were collected and analyzed using histological, radiological, immunohistochemical, and immunofluorescence techniques to assess the tissue repair, osteogenic, and antisenescence effects of rESWT as well as to identify the optimal therapeutic dose. Then, a new set of rats with MIA-induced OA that received rESWT, treadmill exercise, or combined therapy (n = 6 per group) was used to compare the therapeutic effects of the 3 methods on knee OA. For in vitro analysis, the impact of rESWT on senescence biomarkers was further evaluated using TNF-α-stimulated rat-derived osteoblasts (n = 3). Significant increases in osteoblast senescence biomarkers were observed in both human and rat SCB with knee OA. These abnormalities, along with damaged cartilage integrity and SCB microarchitecture, were evident in rats with MIA-induced OA but were alleviated by rESWT, with the optimal dose being 0.096 mJ/mm². Significant mitigations in senescence and cell cycle disturbances were noted in rESWT-treated TNF-α-stimulated osteoblasts in vitro. No significant differences were found between rESWT and treadmill exercise, nor was there any further improvement after combining these 2 treatment methods. In early-stage knee OA, rESWT alleviated SCB abnormalities, reducing osteoblast senescence and stabilizing the cell cycle. rESWT may serve as a supplementary or alternative treatment option, particularly when physical exercise is contraindicated. rESWT alleviated SCB abnormalities and mitigated osteoblast senescence in early-stage OA, making it a potential supplementary treatment approach for some patients with OA.