Low-intensity pulsed ultrasound regulates bone marrow mesenchymal stromal cells differentiation and inhibits bone loss by activating the IL-11-Wnt/β-catenin signaling pathway

• Published in: International immunopharmacology 2024-12, Vol.143 (Pt 1), p.113380, Article 113380
• Main Authors: Han, Yijing, Gao, Hui, Gao, Jing, Yang, Yonghong, He, Chengqi
• Format: Article
• Language: English
• Subjects: Animals; Bone marrow mesenchymal stromal cell; Cell Differentiation; Cells, Cultured; Female; Humans; IL-11; Interleukin-11 - metabolism; Low-intensity pulsed ultrasound; Mesenchymal Stem Cells - metabolism; Mice; Mice, Inbred C57BL; Osteogenesis; Osteoporosis; Osteoporosis - metabolism; Osteoporosis - therapy; Ovariectomy; Ultrasonic Therapy - methods; Ultrasonic Waves; Wnt Signaling Pathway; Wnt/β-Catenin
• ISSN: 1567-5769; 1878-1705; 1878-1705
• DOI: 10.1016/j.intimp.2024.113380

[Display omitted] •LIPUS can promote osteogenic differentiation and inhibiting adipogenic differentiation of BMSCs.•IL-11, which is regulated by LIPUS, mediates the regulation of the Wnt/β-catenin signaling pathway.•LIPUS inhibites bone loss in ovariectomized mice.•LIPUS can regulate BMSCs differentiation and inhibit bone loss by activating the IL-11-Wnt/β-catenin signaling pathway. Osteoporosis (OP) is a common metabolic bone disease. Low-intensity pulsed ultrasound (LIPUS) can effectively promote bone formation and fracture healing. The Wnt/β-catenin signaling pathway is crucial for regulating bone homeostasis and bone diseases, and its downregulation is one of the main mechanisms of osteoporosis pathogenesis. Interleukin-11 (IL-11), which is regulated by mechanical stress, is a key factor in bone remodeling. Here, we investigated the optimal intervention parameters for LIPUS, the relationships among LIPUS, IL-11, and the Wnt/β-catenin signaling pathway, and the effects of LIPUS on bone loss and potential molecular mechanisms in ovariectomized (OVX) mice. Bone marrow mesenchymal stromal cells (BMSCs) were subjected to LIPUS intervention for 0, 10, or 20 min to determine the optimal intervention time. The mediating role of IL-11 in LIPUS intervention was explored through IL-11 knockdown and overexpression. Finally, animal experiments were conducted to investigate the in vivo therapeutic effects of LIPUS. The optimal intervention time for LIPUS was 20 min. LIPUS promoted IL-11 expression and upregulated the Wnt/β-catenin signaling pathway, thereby promoting osteogenic differentiation and inhibiting adipogenic differentiation of BMSCs. IL-11 mediates the regulation of the Wnt/β-catenin signaling pathway by LIPUS. Additionally, LIPUS effectively improved the bone microstructure in ovariectomized mice, inhibited bone loss, promoted IL-11 expression in bone tissue, and activated the Wnt/β-catenin signaling pathway in the femur. Low-intensity pulsed ultrasound can regulate BMSCs differentiation and inhibit bone loss by promoting IL-11 expression and activating the Wnt/β-catenin signaling pathway.