Interleukin-35 Is Involved in Angiogenesis/Bone Remodeling Coupling Through T Helper 17/Interleukin-17 Axis

Frontiers in Endocrinology

Yuxuan Li¹  Hui Zhang²  Jie Yang²  Hui Shen²  Jing Lu²  Lin Yuan²  Liping Xia²  Lutian Yao³ 

[1] Department of Rheumatology and Immunology, Shengjing Hospital of China Medical University, Shenyang, China;Department of Rheumatology and Immunology, The First Affiliated Hospital of China Medical University, Shenyang, China;Department of Sports Medicine and Joint Surgery/Orthopedic, The First Affiliated Hospital of China Medical University, Shenyang, China;

关键词: interleukin-35;    osteoclasts;    bone resorption;    angiogenesis;    osteoporosis;   

DOI  :  10.3389/fendo.2021.642676

来源: DOAJ

【 摘 要 】

ObjectiveOsteoporosis is a common metabolic bone disease mainly involving bone remodeling and blood vessels. The current study aimed to explore the suppressive role of interleukin (IL)-35 in nuclear factor kappa-B ligand receptor activator (RANKL) and macrophage colony stimulating factor (M-CSF)-induced osteoclastogenesis and angiogenesis in osteoclasts.MethodsOsteoclasts differentiation were induced by incubation of mouse leukemic monocyte/macrophage cell line RAW264.7 cells in the presence of RANKL and M-CSF and was assessed with tartrate-resistant acid phosphatase (TRAP) staining assay. The viability and apoptosis of RAW264.7 was measured using CCK-8 assay and flow cytometry, respectively. The expression of angiogenic genes and proteins were measured using RT-PCR, Western blots and ELISA. The inhibition of Th17/IL-17 axis was examined using plumbagin, which was demonstrated as an IL-17A related signaling pathway inhibitor.ResultsIL-35 inhibited the viability of RAW264.7 cells and promoted the apoptosis of RAW264.7 cells in a dose-dependent manner. Furthermore, IL-35 dose-dependently suppressed the expression of angiogenic markers including VEGF and its receptor. The suppressive effect of IL-35 was confirmed through the activation of Th17/IL-17 axis.ConclusionsWe demonstrated for the first time the immuno-suppressive function of IL-35 on RANKL and M-CSF-induced osteoclastogenesis and angiogenesis through Th17/IL-17 axis. Therapeutic approach involving augmentation of IL-35 regulatory response may serve as a novel treatment option for osteoporosis, especially by suppressing bone resorption and angiogenesis.

【 授权许可】

Unknown