Low-Intensity Pulsed Ultrasound Alleviates Osteoarthritis Condition Through Focal Adhesion Kinase–Mediated Chondrocyte Proliferation and Differentiation

Abstract

Objective: Osteoarthritis (OA) is a prevalent chronic multifactorial degenerative disease characterized by joint tissue inflammation, osteophyte formation, subchondral bone sclerosis, and articular cartilage degradation. Low-intensity pulsed ultrasound (LIPUS), a noninvasive ultrasound technique, is widely used to attenuate diseases. The aim of this study was to investigate whether LIPUS can ameliorate OA, and to explore its underlying molecular mechanism. Design: The OA model was established in a C57BL/6 mouse by the anterior cruciate ligament transaction method. OA was assessed using arthritis scoring and weightbearing parameters. Chondrocyte proliferation was detected by a CCK-8 assay. The levels of interleukin-6 (IL-6), IL-8 and tumor necrosis factor-α (TNF-α) in synovial fluid of the mice were measured by enzyme-linked immunosorbent assay. Results: In OA mice, the arthritis score and weightbearing abilities were dramatically improved by LIPUS treatment. LIPUS also remarkably declined the levels of inflammatory cytokines IL-6, IL-8, and TNF-α in synovial fluid of OA mice. Moreover, LIPUS promoted chondrocyte proliferation and differentiation by activating focal adhesion kinase (FAK) signaling. Inhibition of FAK significantly blocked LIPUS-mediated cell proliferation and differentiation in vitro, as well as inflammation condition in OA mice. Conclusion: LIPUS alleviates OA through promoting chondrocytes proliferation and differentiation by activating FAK, which could act as an intervening target for OA treatment.