低强度脉冲超声通过激活 IL-11-Wnt/β-catenin 信号通路调节骨髓间充质基质细胞分化并抑制骨质流失

IF 4.8 2区 医学 Q2 IMMUNOLOGY International immunopharmacology Pub Date : 2024-10-14 DOI:10.1016/j.intimp.2024.113380
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引用次数: 0

摘要

背景骨质疏松症(OP)是一种常见的代谢性骨病。低强度脉冲超声(LIPUS)能有效促进骨形成和骨折愈合。Wnt/β-catenin 信号通路是调节骨稳态和骨病的关键,其下调是骨质疏松症发病的主要机制之一。白细胞介素-11(IL-11)受机械应力调控,是骨重塑的关键因素。方法对骨髓间充质基质细胞(BMSCs)进行0、10或20分钟的LIPUS干预,以确定最佳干预时间。通过IL-11的敲除和过表达,探讨了IL-11在LIPUS干预中的介导作用。结果 LIPUS的最佳干预时间为20分钟。LIPUS促进了IL-11的表达,并上调了Wnt/β-catenin信号通路,从而促进了BMSCs的成骨分化,抑制了其成脂肪分化。IL-11介导了LIPUS对Wnt/β-catenin信号通路的调控。此外,LIPUS 还能有效改善卵巢切除小鼠的骨微结构,抑制骨质流失,促进骨组织中 IL-11 的表达,激活股骨中 Wnt/β-catenin 信号通路。
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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

Background

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.

Methods

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.

Results

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.

Conclusion

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.
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来源期刊
CiteScore
8.40
自引率
3.60%
发文量
935
审稿时长
53 days
期刊介绍: International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.
期刊最新文献
Corrigendum to "Artesunate ameliorates ligature-induced periodontitis by attenuating NLRP3 inflammasome-mediated osteoclastogenesis and enhancing osteogenic differentiation" [Int. Immunopharmacol. 123 (2023) 110749]. Corrigendum to "Human placental mesenchymal stromal cells modulate IFN-γ and IL-10 secretion by CD4+T cells via CD73, and alleviate intestinal damage in mice with graft-versus-host disease" [Int. Immunopharmacol. 124 (2023) 110767]. Corrigendum to "IL-32 aggravates metabolic disturbance in human nucleus pulposus cells by activating FAT4-mediated Hippo/YAP signaling" [Int. Immunopharmacol. 141 (2024) 112966]. Corrigendum to "LncRNA THUMPD3-AS1 enhances the proliferation and inflammatory response of chondrocytes in osteoarthritis" [Int. Immunopharmacol. 100 (2021) 108138]. Corrigendum to "Secretory Nogo-B regulates Th2 differentiation in the lung cancer microenvironment" [Int. Immunopharmacol. 140 (2024) 112763].
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